Broad-spectrum therapeutic suppression of metastatic melanoma through nuclear hormone receptor activation
Open accessAbstract
Melanoma metastasis is a devastating outcome lacking an effective preventative therapeutic. We provide pharmacologic, molecular, and genetic evidence establishing the liver-X nuclear hormone receptor (LXR) as a therapeutic target in melanoma. Oral administration of multiple LXR agonists suppressed melanoma invasion, angiogenesis, tumor progression, and metastasis. Molecular and genetic experiments revealed these effects to be mediated by LXRβ, which elicits these outcomes through transcriptional induction of tumoral and stromal apolipoprotein-E (ApoE). LXRβ agonism robustly suppressed tumor growth and metastasis across a diverse mutational spectrum of melanoma lines. LXRβ targeting significantly prolonged animal survival, suppressed the progression of established metastases, and inhibited brain metastatic colonization. Importantly, LXRβ activation displayed melanoma-suppressive cooperativity with the frontline regimens dacarbazine, B-Raf inhibition, and the anti-CTLA-4 antibody and robustly inhibited melanomas that had acquired resistance to B-Raf inhibition or dacarbazine. We present a promising therapeutic approach that uniquely acts by transcriptionally activating a metastasis suppressor gene.
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Pharmacological activation of LXRβ suppresses melanoma tumor progression and metastatic colonization, effects caused by ApoE-mediated suppression of pro-metastatic invasion and endothelial recruitment phenotypes.
“pharmacological activation of the ubiquitously expressed LXRβ isoform was found to suppress melanoma tumor progression and metastatic colonization—effects caused by ApoE-mediated suppression of pro-metastatic invasion and endothelial recruitment phenotypes”
From LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer (2018) · cites this paper as Pencheva et al., 2014
The anti-tumor effects of LXR agonists are mediated by LXRβ and its transcriptional target Apoe.
“We had previously shown that the anti-tumor effects of LXR agonists were mediated by the ubiquitously expressed LXRβ nuclear hormone receptor and its transcriptional target Apoe”
From LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer (2018) · cites this paper as Pencheva et al., 2014
Tumoral and stroma-derived APOE suppresses melanoma progression.
“We previously reported that tumoral and stroma-derived APOE suppresses melanoma progression4,12,13.”
From Common germline variants of the human APOE gene modulate melanoma progression and survival (2020) · cites this paper as [13]
Both tumor-derived and stroma-derived APOE regulate melanoma metastatic capacity via extracellular action on tumoral APOE receptors.
“APOE protein is known to act extracellularly on tumoral APOE receptors, and both tumor-derived and stroma-derived APOE have been found to regulate melanoma metastatic capacity in this manner (4,5).”
From Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression and Metastasis (2023) · cites this paper as [5]
APOE protein acts extracellularly on tumoral APOE receptors.
“APOE protein is known to act extracellularly on tumoral APOE receptors, and both tumor-derived and stroma-derived APOE have been found to regulate melanoma metastatic capacity in this manner (4,5).”
From Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression and Metastasis (2023) · cites this paper as [5]
Cites
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · see citing works
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155 · see citing works
Improved survival with vemurafenib in melanoma with BRAF V600E mutation
Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103782 · Cited by 7,720 · see citing works
Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy
Scher, H. I., Fizazi, K., Saad, F., Taplin, M.-E., Sternberg, C. N., Miller, K., de Wit, R., Mulders, P., Chi, K. N., Shore, N. D., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1207506 · Cited by 4,586 · see citing works
Cancer Metastasis: Building a Framework
Gupta, G. P., & Massagué, J. (2006) · Cell · doi:10.1016/j.cell.2006.11.001 · Cited by 4,230 · see citing works
Genes that mediate breast cancer metastasis to lung
Minn, A. J., Gupta, G. P., Siegel, P. M., Bos, P. D., Shu, W., Giri, D. D., Viale, A., Olshen, A. B., Gerald, W. L., & Massagué, J. (2005) · Nature · doi:10.1038/nature03799 · Cited by 2,922 · see citing works
A landscape of driver mutations in melanoma
Hodis, E., Watson, I. R., Kryukov, G. V., Arold, S. T., Imielinski, M., Theurillat, J.-P., Nickerson, E., Auclair, D., Li, L., Place, C., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.024 · Cited by 2,610 · see citing works
Tumour invasion and metastasis initiated by microRNA-10b in breast cancer
Ma, L., Teruya-Feldstein, J., & Weinberg, R. A. (2007) · Nature · doi:10.1038/nature06174 · Cited by 2,605 · see citing works
A multigenic program mediating breast cancer metastasis to bone
Kang, Y., Siegel, P. M., Shu, W., Drobnjak, M., Käkönen, S.-M., Cordon‐Cardo, C., Guise, T. A., & Massagué, J. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00132-6 · Cited by 2,562 · see citing works
Development of a second-generation antiandrogen for treatment of advanced prostate cancer.
Tran, C., Ouk, S., Clegg, N. J., Chen, Y., Watson, P. A., Arora, V., Wongvipat, J., Smith-Jones, P. M., Yoo, D., Kwon, A., et al. (2009) · Science · doi:10.1126/science.1168175 · Cited by 2,292 · see citing works
Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M., Attar, N., Sazegar, H., et al. (2010) · Nature · doi:10.1038/nature09626 · Cited by 2,177 · see citing works
Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib
Sosman, J. A., Kim, K. B., Schuchter, L., Gonzalez, R., Pavlick, A. C., Weber, J. S., McArthur, G. A., Hutson, T. E., Moschos, S. J., Flaherty, K. T., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1112302 · Cited by 2,156 · see citing works
Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR
Prahallad, A., Sun, C., Huang, S., Di Nicolantonio, F., Salazar, R., Zecchin, D., Beijersbergen, R. L., Bardelli, A., & Bernards, R. (2012) · Nature · doi:10.1038/nature10868 · Cited by 2,051 · see citing works
Endogenous human microRNAs that suppress breast cancer metastasis
Tavazoie, S. F., Alarcón, C. R., Óskarsson, T., Padua, D. M., Wang, Q., Bos, P. D., Gerald, W. L., & Massagué, J. (2008) · Nature · doi:10.1038/nature06487 · Cited by 1,858 · see citing works
Self-citationAn oxysterol signalling pathway mediated by the nuclear receptor LXRα
Janowski, B. A., Willy, P. J., Devi, T. R., Falck, J. R., & Mangelsdorf, D. J. (1996) · Nature · doi:10.1038/383728a0 · Cited by 1,754 · see citing works
RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
Poulikakos, P. I., Persaud, Y., Janakiraman, M., Kong, X., Ng, C., Moriceau, G., Shi, H., Atefi, M., Titz, B., Gabay, M. T., et al. (2011) · Nature · doi:10.1038/nature10662 · Cited by 1,454 · see citing works
BrafV600E cooperates with Pten loss to induce metastatic melanoma
Dankort, D., Curley, D. P., Cartlidge, R. A., Nelson, B., Karnezis, A. N., Damsky Jr, W. E., You, M. J., DePinho, R. A., McMahon, M., & Bosenberg, M. (2009) · Nature Genetics · doi:10.1038/ng.356 · Cited by 1,189 · see citing works
AACR Centennial Series: The Biology of Cancer Metastasis: Historical Perspective
Talmadge, J. E., & Fidler, I. J. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1040 · Cited by 1,172 · see citing works
LXR, a nuclear receptor that defines a distinct retinoid response pathway.Preprint
Willy, P. J., Umesono, K., Ong, E. S., Evans, R. M., Heyman, R. A., & Mangelsdorf, D. J. (1995) · Genes & Development · doi:10.1101/gad.9.9.1033 · Cited by 1,124 · see citing works
O'Hare, T., Walters, D. K., Stoffregen, E. P., Jia, T., Manley, P. W., Mestan, J., Cowan-Jacob, S. W., Lee, F. Y., Heinrich, M. C., Deininger, M. W. N., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0259 · Cited by 1,036 · see citing works
van Elsas, A., Hurwitz, A. A., & Allison, J. P. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.3.355 · Cited by 1,020 · see citing works
27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology
Nelson, E. R., Wardell, S., Jasper, J. S., Park, S., Suchindran, S., Howe, M. K., Carver, N. J., Pillai, R. V., Sullivan, P., Sondhi, V., et al. (2013) · Science · doi:10.1126/science.1241908 · Cited by 805 · see citing works
LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes
Laffitte, B. A., Repa, J. J., Joseph, S. B., Wilpitz, D. C., Kast, H. R., Mangelsdorf, D. J., & Tontonoz, P. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.2.507 · Cited by 683 · see citing works
Shi, H., Moriceau, G., Kong, X., Lee, M., Lee, H., Koya, R. C., Ng, C., Chodon, T., Scolyer, R. A., Dahlman, K. B., et al. (2012) · Nature Communications · doi:10.1038/ncomms1727 · Cited by 637 · see citing works
Systematic Review of Medical Treatment in Melanoma: Current Status and Future Prospects
Garbe, C., Eigentler, T., Keilholz, U., Hauschild, A., & Kirkwood, J. M. (2011) · The Oncologist · doi:10.1634/theoncologist.2010-0190 · Cited by 581 · see citing works
Treatment of metastatic melanoma: an overview.
Bhatia, S., Tykodi, S. S., & Thompson, J. A. (2009) · PubMed · Cited by 531 · see citing works
A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells
Png, K. J., Halberg, N., Yoshida, M., & Tavazoie, S. F. (2011) · Nature · doi:10.1038/nature10661 · Cited by 531 · see citing works
Self-citationCollins, J. L., Fivush, A. M., Watson, M. A., Galardi, C. M., Lewis, M. C., Moore, L. B., Parks, D. J., Wilson, J. G., Tippin, T. K., Binz, J. G., et al. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm0255116 · Cited by 437 · see citing works
Pencheva, N., Tran, H., Buss, C., Huh, D., Drobnjak, M., Busam, K., & Tavazoie, S. F. (2012) · Cell · doi:10.1016/j.cell.2012.10.028 · Cited by 415 · see citing works
Self-citationYang, H. Y., Higgins, B., Kolinsky, K. D., Packman, K. E., Go, Z., Iyer, R. M., Kolis, S. P., Zhao, S., Lee, R., Grippo, J. F., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0646 · Cited by 404 · see citing works
Apfel, R., Benbrook, D., Lernhardt, E., Ortiz, M. A., Salbert, G., & Pfahl, M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.10.7025 · Cited by 372 · see citing works
Ponomarev, V., Doubrovin, M., Serganova, I. S., Vider, J., Shavrin, A., Beresten, T., Ivanova, A. E., Ageyeva, L., Tourkova, V., Balatoni, J., et al. (2004) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-003-1441-5 · Cited by 286 · see citing works
Song, C., Kokontis, J. M., Hiipakka, R. A., & Liao, S. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.10809 · Cited by 256 · see citing works
Mak, P. A., Laffitte, B. A., Desrumaux, C. M., Joseph, S. B., Curtiss, L. K., Mangelsdorf, D. J., Tontonoz, P., & Edwards, P. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202993200 · Cited by 244 · see citing works
A Nuclear Receptor Atlas: 3T3-L1 Adipogenesis
Fu, M., Sun, T., Bookout, A. L., Downes, M., Yu, R. T., Evans, R. M., & Mangelsdorf, D. J. (2005) · Molecular Endocrinology · doi:10.1210/me.2004-0539 · Cited by 233 · see citing works
Oestrogen-related receptors in breast cancer: control of cellular metabolism and beyond
Deblois, G., & Giguère, V. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3396 · Cited by 226 · see citing works
Synthetic LXR agonists increase LDL in CETP species
Groot, P. H. E., Pearce, N. J., Yates, J. W., Stocker, C. J., Sauermelch, C. F., Doe, C. P. A., Willette, R. N., Olzinski, A. R., Peters, T., d'Epagnier, D. L., et al. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m500116-jlr200 · Cited by 120 · see citing works
Holbeck, S. L., Chang, J., Best, A. M., Bookout, A. L., Mangelsdorf, D. J., & Martinez, E. D. (2010) · Molecular Endocrinology · doi:10.1210/me.2010-0040 · Cited by 71 · see citing works
Pollack, V. A., & Fidler, I. J. (1982) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/69.1.137 · Cited by 41 · see citing works
Pollack, V. A., & Fidler, I. J. (1982) · The Mouseion at the JAXlibrary (Jackson Laboratory) · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Harnessing innate immunity in cancer therapy
Demaria, O., Cornen, S., Daëron, M., Morel, Y., Medzhitov, R., & Vivier, E. (2019) · Nature · doi:10.1038/s41586-019-1593-5 · Cited by 957 · see citing works
STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity
Demaria, O., Gassart, A. D., Coso, S., Gestermann, N., Domizio, J. D., Flatz, L., Gaide, O., Michielin, O. A., Hwu, P., Petrova, T. V., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1512832112 · Cited by 574 · see citing works
LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer
Tavazoie, M. F., Pollack, I., Tanqueco, R., Ostendorf, B. N., Reis, B. S., Gonsalves, F. C., Kurth, I., Andreu-Agullo, C., Derbyshire, M. L., Posada, J., et al. (2018) · Cell · doi:10.1016/j.cell.2017.12.026 · Cited by 476 · see citing works
“LXR Activation Suppresses Tumor Growth and Reduces MDSC Abundance We had previously observed that pharmacological activation of LXR using the LXRb-selective agonist GW3965 suppressed melanoma angiogenesis, tumor growth, and metastatic colonization (Pencheva et al., 2014).”
InfluentialSelf-citationLin, H., Liu, C., Hu, A.-K., Zhang, D., Yang, H., & Mao, Y. Q. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01544-7 · Cited by 424 · see citing works
Lipid metabolism in cancer progression and therapeutic strategies
Fu, Y., Zou, T., Shen, X., Nelson, P. J., Li, J., Wu, C., Yang, J., Zheng, Y., Bruns, C. J., Zhao, Y., et al. (2020) · MedComm · doi:10.1002/mco2.27 · Cited by 406 · see citing works
Loeuillard, E. J., Yang, J., Buckarma, E. H., Wang, J., Liu, Y., Conboy, C. B., Pavelko, K. D., Li, Y., O’Brien, D. R., Wang, C., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci137110 · Cited by 370 · see citing works
A framework for the development of effective anti-metastatic agents
Anderson, R. L., Balasas, T., Callaghan, J., Coombes, R. C., EVANS, J., Hall, J. A., Kinrade, S. A., Jones, D., Jones, P. S., Jones, R. J., et al. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0134-8 · Cited by 341 · see citing works
An LXR-Cholesterol Axis Creates a Metabolic Co-Dependency for Brain Cancers
Villa, G. R., Hulce, J. J., Zanca, C., Bi, J., Ikegami, S., Cahill, G. L., Gu, Y., Lum, K. M., Masui, K., Yang, H., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.09.008 · Cited by 327 · see citing works
Fang, R., Chen, X., Zhang, S., Shi, H., Ye, Y., Shi, H., Zou, Z., Li, P., Guo, Q., Ma, L., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20379-7 · Cited by 315 · see citing works
The Evolving Landscape of Brain Metastasis
Valiente, M., Ahluwalia, M. S., Boire, A. A., Brastianos, P. K., Goldberg, S. B., Lee, E. Q., Rhun, É. L., Preusser, M., Winkler, F., & Soffietti, R. (2018) · Trends in cancer · doi:10.1016/j.trecan.2018.01.003 · Cited by 310 · see citing works
Contradictory roles of lipid metabolism in immune response within the tumor microenvironment
Yu, W., Lei, Q., Yang, L., Qin, G., Liu, S., Wang, D., Ping, Y., & Zhang, Y. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01200-4 · Cited by 272 · see citing works
Bertero, T., Cottrill, K. A., Lu, Y., Haeger, C. M., Dieffenbach, P. B., Annis, S., Hale, A., Bhat, B., Kaimal, V., Zhang, Y., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.09.049 · Cited by 232 · see citing works
Myeloid-Derived Suppressor Cells in the Tumor Microenvironment
Dysthe, M., & Parihar, R. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-35723-8_8 · Cited by 210 · see citing works
Uncoupling Nuclear Receptor LXR and Cholesterol Metabolism in Cancer
Bovenga, F., Sabbà, C., & Moschetta, A. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.03.002 · Cited by 209 · see citing works
A PGC1α-mediated transcriptional axis suppresses melanoma metastasis
Luo, C., Lim, J.-H., Lee, Y., Granter, S. R., Thomas, A., Vázquez, F., Widlund, H. R., & Puigserver, P. (2016) · Nature · doi:10.1038/nature19347 · Cited by 205 · see citing works
Laurette, P., Strub, T., Koludrović, D., Keime, C., Gras, S. L., Seberg, H., Otterloo, E. V., Imrichová, H., Siddaway, R., Aerts, S., et al. (2015) · eLife · doi:10.7554/elife.06857 · Cited by 189 · see citing works
Cholesterol and breast cancer pathophysiology
Nelson, E. R., Chang, C.-Y., & McDonnell, D. P. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.10.001 · Cited by 188 · see citing works
Targeting liver X receptors in cancer therapeutics
Lin, C., & Gustafsson, J.-Α. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3912 · Cited by 174 · see citing works
Cholesterol and beyond - The role of the mevalonate pathway in cancer biology
Göbel, A., Rauner, M., Hofbauer, L. C., & Rachner, T. D. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188351 · Cited by 167 · see citing works
Donadon, M., Torzilli, G., Cortese, N., Soldani, C., di Tommaso, L., Franceschini, B., Carriero, R., Barbagallo, M., Rigamonti, A., Anselmo, A., et al. (2020) · Journal of Experimental Medicine · doi:10.1084/jem.20191847 · Cited by 142 · see citing works
Nuclear receptors: recent drug discovery for cancer therapies.
Zhao, L.-J., Zhou, S.-T., & Gustafsson, J. (2019) · Endocrine reviews · doi:10.1210/er.2018-00222 · Cited by 137 · see citing works
Role of Cholesterol and Lipid Rafts in Cancer Signaling: A Promising Therapeutic Opportunity?
Vona, R., Iessi, E., & Matarrese, P. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.622908 · Cited by 161 · see citing works
Mechanisms of Acquired BRAF Inhibitor Resistance in Melanoma: A Systematic Review
Proietti, I., Skroza, N., Bernardini, N., Tolino, E., Balduzzi, V., Marchesiello, A., Michelini, S., Volpe, S., Mambrin, A., Mangino, G., et al. (2020) · Cancers · doi:10.3390/cancers12102801 · Cited by 146 · see citing works
Dendrogenin A drives LXR to trigger lethal autophagy in cancers
Segala, G., David, M., de Medina, P., Poirot, M. C., Serhan, N., Vergez, F., Mougel, A., Saland, E., Carayon, K., Leignadier, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01948-9 · Cited by 125 · see citing works
Imbert, C., Montfort, A., Fraisse, M., Marcheteau, E., Gilhodes, J., Martin, E., Bertrand, F. A., Marcellin, M., Burlet‐Schiltz, O., de Peredo, A. G., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14218-7 · Cited by 124 · see citing works
Brain Metastasis Cell Lines Panel: A Public Resource of Organotropic Cell Lines
Valiente, M., Swearingen, A. E. D. V., Anders, C. K., Bairoch, A., Boire, A. A., Bos, P. D., Cittelly, D. M., Erez, N., Ferraro, G. B., Fukumura, D., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-0291 · Cited by 123 · see citing works
Reactive Astrocytes in Brain Metastasis
Wasilewski, D., Priego, N., Torre, C. F., & Valiente, M. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00298 · Cited by 121 · see citing works
Giacomini, I., Gianfanti, F., Desbats, M. A., Orso, G., Berretta, M., Prayer‐Galetti, T., Ragazzi, E., & Cocetta, V. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.682911 · Cited by 120 · see citing works
CYP27A1 Loss Dysregulates Cholesterol Homeostasis in Prostate Cancer
Alfaqih, M. A., Nelson, E. R., Liu, W., Safi, R., Jasper, J. S., Macias, E., Geradts, J., Thompson, J. W., Dubois, L. G., Freeman, M. R., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2738 · Cited by 117 · see citing works
Blocking Tumor Necrosis Factor α Enhances CD8 T-cell–Dependent Immunity in Experimental Melanoma
Bertrand, F., Rochotte, J., Colacios, C., Montfort, A., Tilkin-Mariamé, A.-F., Touriol, C., Rochaix, P., Lajoie-Mazenc, I., Andrieu-Abadie, N., Levade, T., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2524 · Cited by 113 · see citing works
Common germline variants of the human APOE gene modulate melanoma progression and survival
Ostendorf, B. N., Bilanovic, J., Adaku, N., Tafreshian, K. N., Tavora, B., Vaughan, R. D., & Tavazoie, S. F. (2020) · Nature Medicine · doi:10.1038/s41591-020-0879-3 · Cited by 108 · see citing works
Self-citationLigands of Therapeutic Utility for the Liver X Receptors
Komati, R., Spadoni, D., Zheng, S., Sridhar, J., Riley, K. E., & Wang, G. (2017) · Molecules · doi:10.3390/molecules22010088 · Cited by 101 · see citing works
Dysregulation of cholesterol metabolism in cancer progression
Liu, X., Lv, M., Zhang, W., & Zhan, Q. (2023) · Oncogene · doi:10.1038/s41388-023-02836-x · Cited by 102 · see citing works
Endogenous Sterol Metabolites Regulate Growth of EGFR/KRAS-Dependent Tumors via LXR
Gabitova, L., Restifo, D., Gorin, A. A., Manocha, K., Handorf, E. A., Yang, D., Cai, K. Q., Klein–Szanto, A. J., Cunningham, D., Kratz, L. E., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.08.023 · Cited by 82 · see citing works
Lipid metabolic Reprogramming: Role in Melanoma Progression and Therapeutic Perspectives
Pellerin, L., Carrié, L., Dufau, C., Nieto, L., Ségui, B., Levade, T., Riond, J., & Andrieu‐Abadie, N. (2020) · Cancers · doi:10.3390/cancers12113147 · Cited by 82 · see citing works
Immunotherapy of targeting MDSCs in tumor microenvironment
Sui, H., Dongye, S., Liu, X., Xu, X., Wang, L., Jin, C. Q., Yao, M., Gong, Z., Jiang, D., Zhang, K., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.990463 · Cited by 80 · see citing works
The Contribution of Cholesterol and its Metabolites to the Pathophysiology of Breast Cancer
Baek, A., & Nelson, E. R. (2016) · Hormones & cancer · doi:10.1007/s12672-016-0262-5 · Cited by 66 · see citing works
Role of cholesterol homeostasis and its efflux pathways in cancer progression
Sharma, B., & Agnihotri, N. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105377 · Cited by 69 · see citing works
Piccinin, E., Cariello, M., & Moschetta, A. (2020) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2020.100933 · Cited by 67 · see citing works
Bertero, T., Cottrill, K. A., Annis, S., Bhat, B., Gochuico, B. R., Osorio, J. C., Rosas, I. O., Haley, K. J., Corey, K. E., Chung, R. T., et al. (2015) · Scientific Reports · doi:10.1038/srep18277 · Cited by 65 · see citing works
Emerging role of liver X receptors in cardiac pathophysiology and heart failure
Cannon, M. V., van Gilst, W. H., & de Boer, R. A. (2015) · Basic Research in Cardiology · doi:10.1007/s00395-015-0520-7 · Cited by 63 · see citing works
Immunomodulatory‐Photodynamic Nanostimulators for Invoking Pyroptosis to Augment Tumor Immunotherapy
Qiu, W., Su, W., Xu, J., Liang, M., Ma, X., Xue, P., Kang, Y., Sun, Z., & Xu, Z. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202201233 · Cited by 63 · see citing works
Hofer, F., Sario, G. D., Musiu, C., Sartoris, S., Sanctis, F. D., & Ugel, S. (2021) · Cells · doi:10.3390/cells10102700 · Cited by 59 · see citing works
Wu, L., Li, L., Li, S., Liu, L., Xin, W., Li, C., Yin, X., Xu, X., Bao, F., & Hua, Z. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.05.006 · Cited by 63 · see citing works
Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities
Jiang, W. G., Jin, W., & Xu, A. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.92274 · Cited by 65 · see citing works
Impact of BRAF mutation status in the prognosis of cutaneous melanoma: an area of ongoing research.
Bhatia, P., Friedlander, P. L., Elmageed, Z. A., & Kandil, E. H. (2015) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2305-5839.2014.12.05 · Cited by 61 · see citing works
LXRα activation and Raf inhibition trigger lethal lipotoxicity in liver cancer
Rudalska, R., Harbig, J., Snaebjornsson, M. T., Klotz, S., Zwirner, S., Taranets, L., Heinzmann, F., Kronenberger, T., Förster, M., Cui, W., et al. (2021) · Nature Cancer · doi:10.1038/s43018-020-00168-3 · Cited by 59 · see citing works
Host CYP27A1 expression is essential for ovarian cancer progression.
He, S.-S., Ma, L., Baek, A., Vardanyan, A., Vembar, V., Chen, J. J., Nelson, A. T., Burdette, J. E., & Nelson, E. R. (2019) · Endocrine-Related Cancer · doi:10.1530/erc-18-0572 · Cited by 49 · see citing works
Metabolic reprograming of MDSCs within tumor microenvironment and targeting for cancer immunotherapy
Li, Q., & Xiang, M. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-021-00776-4 · Cited by 54 · see citing works
The Medicinal Chemistry of Liver X Receptor (LXR) Modulators
Tice, C. M., Noto, P. B., Fan, K. Y., Zhuang, L., Lala, D. S., & Singh, S. B. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500442z · Cited by 53 · see citing works
25-Hydroxycholesterol promotes migration and invasion of lung adenocarcinoma cells
Chen, L., Zhang, L., Xian, G., Lv, Y., Lin, Y., & Wang, Y. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.02.003 · Cited by 52 · see citing works
Obesity and the Impact on Cutaneous Melanoma: Friend or Foe?
Smith, L. K., Arabi, S., Lelliott, E. J., McArthur, G. A., & Sheppard, K. E. (2020) · Cancers · doi:10.3390/cancers12061583 · Cited by 53 · see citing works
Neutral Sphingomyelinase 2 Heightens Anti-Melanoma Immune Responses and Anti–PD-1 Therapy Efficacy
Montfort, A., Bertrand, F. A., Rochotte, J., Gilhodes, J., Filleron, T., Milhès, J., Dufau, C., Imbert, C., Riond, J., Tosolini, M., et al. (2021) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0342 · Cited by 52 · see citing works
Cholesterol-Lowering Phytochemicals: Targeting the Mevalonate Pathway for Anticancer Interventions
Laka, K., Makgoo, L., & Mbita, Z. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.841639 · Cited by 51 · see citing works
Activation of LXRβ inhibits tumor respiration and is synthetically lethal with Bcl‐xL inhibition
Nguyen, T. T. T., Ishida, C. T., Shang, E., Shu, C., Torrini, C., Zhang, Y., Bianchetti, E., Sanchez‐Quintero, M. J., Kleiner, G., Quinzii, C. M., et al. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201910769 · Cited by 50 · see citing works
Carbó, J. M., León, T. E., Font-Díaz, J., de la Rosa, J. V., Castrillo, A., Picard, F. S. R., Staudenraus, D., Huber, M., Cedó, L., Escolá‐Gil, J. C., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-3360 · Cited by 50 · see citing works
Burris, T. P., de Vera, I. M. S., Côté, I., Flaveny, C. A., Wanninayake, U. S., Chatterjee, A., Walker, J. K., Steinauer, N., Zhang, J., Coons, L. A., et al. (2023) · Pharmacological Reviews · doi:10.1124/pharmrev.121.000436 · Cited by 53 · see citing works
Li, M., Jiang, P., Wei, S., Wang, J., & Li, C. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1113312 · Cited by 50 · see citing works
Targeting cholesterol homeostasis in hematopoietic malignancies
Brendolan, A., & Russo, V. E. A. (2021) · Blood · doi:10.1182/blood.2021012788 · Cited by 48 · see citing works
Recent Advances in the Medicinal Chemistry of Liver X Receptors.
Elgendy, B., Goher, S. S., Hegazy, L., Arief, M., & Burris, T. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00045 · Cited by 46 · see citing works
Sterol Metabolism and Transport in Atherosclerosis and Cancer
Yamauchi, Y., & Rogers, M. A. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00509 · Cited by 48 · see citing works
Lamch, Ł., Kulbacka, J., Pietkiewicz, J., Rossowska, J., Dubińska–Magiera, M., Choromańska, A., & Wilk, K. A. (2016) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/j.jphotobiol.2016.04.018 · Cited by 47 · see citing works
Wan, D., Yang, Y., Liu, Y., Cun, X., Li, M., Xu, S., Zhao, W., Xiang, Y., Qiu, Y., Yu, Q., et al. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.11.011 · Cited by 45 · see citing works
Font-Díaz, J., Jiménez‐Panizo, A., Caelles, C., Vivanco, M. D., Pérez, P., Aranda, A., Estébanez‐Perpiñá, E., Castrillo, A., Ricote, M., & Valledor, A. F. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.12.007 · Cited by 45 · see citing works
Exploring the Impact of the Obesity Paradox on Lung Cancer and Other Malignancies
Nitsche, L., Mukherjee, S., Cheruvu, K., Krabak, C., Rachala, R., Ratnakaram, K., Sharma, P., Singh, M., & Yendamuri, S. (2022) · Cancers · doi:10.3390/cancers14061440 · Cited by 45 · see citing works
Kaneko, T., Kanno, C., Ichikawa‐Tomikawa, N., Kashiwagi, K., Yaginuma, N., Ohkoshi, C., Tanaka, M., Sugino, T., Imura, T., Hasegawa, H., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5428 · Cited by 44 · see citing works
The emerging roles of liver X receptors and their ligands in cancer
Lin, C.-Y., Vedin, L.-L., & Steffensen, K. (2016) · Expert opinion on therapeutic targets · doi:10.1517/14728222.2015.1081169 · Cited by 40 · see citing works
Targeting the tumor microenvironment in cholangiocarcinoma: implications for therapy
Wang, J., & Ilyas, S. I. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2021.1865308 · Cited by 38 · see citing works
Nuclear Receptors in Cancer Inflammation and Immunity
Zhao, L., Hu, H., Gustafsson, J.-Α., & Zhou, S. (2020) · Trends in Immunology · doi:10.1016/j.it.2019.12.006 · Cited by 36 · see citing works
Watts, J. A., Grunseich, C., Rodriguez, Y., Liu, Y., Li, D., Burdick, J. T., Bruzel, A., Crouch, R. J., Mahley, R. W., Wilson, S. H., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac1107 · Cited by 37 · see citing works
Feng, K., Ma, C., Liu, Y., Yang, X., Yang, Z., Chen, Y., Xu, T., Yang, C., Zhang, S., Li, Q., et al. (2021) · Theranostics · doi:10.7150/thno.53139 · Cited by 35 · see citing works
The estrogen receptor as a mediator of the pathological actions of cholesterol in breast cancer
McDonnell, D. P., Chang, C.-Y., & Nelson, E. R. (2014) · Climacteric · doi:10.3109/13697137.2014.966949 · Cited by 33 · see citing works
Fakih, O., Sanver, D., Kane, D., & Thorne, J. L. (2018) · Biochimie · doi:10.1016/j.biochi.2018.04.028 · Cited by 33 · see citing works
Liver X receptors as potential targets for cancer therapeutics (Review)
Ju, X., Huang, P., Chen, M., & Wang, Q. (2017) · Oncology Letters · doi:10.3892/ol.2017.7259 · Cited by 32 · see citing works
Shao, W., Zhu, W., Lin, J., Luo, M., Lin, Z., Lu, L., Jia, H., Qin, L., Lü, M., & Chen, J. (2019) · Neoplasia · doi:10.1016/j.neo.2019.08.002 · Cited by 30 · see citing works
Miller, A. L., Garcia, P. L., Fehling, S. C., Gamblin, T. L., Vance, R. B., Chen, D., Yang, E. S.-H., van Waardenburg, R. C. A. M., & Yoon, K. J. (2021) · Cancers · doi:10.3390/cancers13143470 · Cited by 30 · see citing works
Lung cancer and obesity: A contentious relationship (Review)
GEORGAKOPOULOU, V. E., Lempesis, I. G., Τράκας, Ν., Sklapani, P., He, Y., & Spandidos, D. A. (2024) · Oncology Reports · doi:10.3892/or.2024.8817 · Cited by 30 · see citing works
de la Aleja, A. G., Herrero, C., Torres‐Torresano, M., Schiaffino, M. T., del Castillo, A., Alonso, B., Vega, M. A., Puig‐Kröger, A., Castrillo, A., & Corbí, A. L. (2023) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-023-04745-4 · Cited by 27 · see citing works
Liver X receptor as a drug target for the treatment of breast cancer
Wu, Y., Yu, D., Yan, D., Hu, Y., Chen, D., Liu, Y., Zhang, H.-D., Yu, S., Cao, H.-X., & Feng, J. (2016) · Anti-Cancer Drugs · doi:10.1097/cad.0000000000000348 · Cited by 27 · see citing works
Yin, K., & Smith, A. G. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2329-4 · Cited by 27 · see citing works
Wang, Q., Sun, L., Yang, X., Ma, X., Li, Q., Chen, Y., Liu, Y., Zhang, D., Li, X., Xiang, R., et al. (2016) · Scientific Reports · doi:10.1038/srep27295 · Cited by 26 · see citing works
Discovery of new LXRβ agonists as glioblastoma inhibitors
Chen, H., Chen, Z., Zhang, Z., Li, Y., Zhang, S.-S., Jiang, F., Wei, J., Ding, P., Zhou, H., Gu, Q., et al. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112240 · Cited by 26 · see citing works
Secreted Apoe rewires melanoma cell state vulnerability to ferroptosis
More, S., Bonnereau, J., Wouters, D., Spotbeen, X., Karras, P., Rizzollo, F., Killian, T., Venken, T., Naulaerts, S., Vervoort, E., et al. (2024) · Science Advances · doi:10.1126/sciadv.adp6164 · Cited by 25 · see citing works
Transcriptional repression of IFNβ1 by ATF2 confers melanoma resistance to therapy
Lau, E., Šedý, J. R., Sander, C., Shaw, M. A., Feng, Y., Scortegagna, M., Claps, G., Robinson, S. E., Cheng, P. F., Srivas, R., et al. (2015) · Oncogene · doi:10.1038/onc.2015.22 · Cited by 25 · see citing works
Ramalingam, P. S., Elangovan, S., Ramaiah, M. J., & Arumugam, S. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1386102 · Cited by 25 · see citing works
Genome-wide analysis of canine oral malignant melanoma metastasis-associated gene expression
Blacklock, K. B., Birand, Z., Selmic, L. E., Nelissen, P., Murphy, S., Blackwood, L., Bass, J., McKay, J., Fox, R. I., Beaver, S., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-42839-x · Cited by 26 · see citing works
Xiong, H., Zhang, Y., Chen, S., Ni, Z., He, J., Li, X., Li, B., Zhao, K., Yang, F., Zeng, Y., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.19321 · Cited by 24 · see citing works
Moresco, M. A., Raccosta, L., Corna, G., Maggioni, D., Soncini, M., Bicciato, S., Doglioni, C., & Russo, V. E. A. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02251 · Cited by 24 · see citing works
Development of novel liver X receptor modulators based on a 1,2,4-triazole scaffold
Goher, S. S., Griffett, K., Hegazy, L., Elagawany, M., Arief, M. M. H., Avdagic, A., Banerjee, S., Burris, T. P., & Elgendy, B. (2018) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2018.12.025 · Cited by 24 · see citing works
Activation of LXR Receptors and Inhibition of TRAP1 Causes Synthetic Lethality in Solid Tumors
Nguyen, T. T. T., Ishida, C. T., Shang, E., Shu, C., Bianchetti, E., Karpel‐Massler, G., & Siegelin, M. D. (2019) · Cancers · doi:10.3390/cancers11060788 · Cited by 23 · see citing works
Chen, T., Xu, J., & Fu, W. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01688 · Cited by 23 · see citing works
Cholesterol metabolites and tumor microenvironment: the road towards clinical translation
Raccosta, L., Fontana, R., Corna, G., Maggioni, D., Moresco, M. A., & Russo, V. E. A. (2015) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-015-1779-0 · Cited by 23 · see citing works
Engineering strategies of sequential drug delivery systems for combination tumor immunotherapy
Xu, Z., Liu, S., Li, Y., Wu, Y., Tu, J., Chen, Q., & Sun, C. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.05.039 · Cited by 22 · see citing works
Suppression of Ca2+ signaling enhances melanoma progression
Gross, S., Hooper, R., Tomar, D., Armstead, A. P., Shanas, N., Mallu, P., Joshi, H., Ray, S., Chong, P. L., Astsaturov, I. A., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2021110046 · Cited by 19 · see citing works
Hutchinson, P. E., & Pringle, J. H. (2022) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.13040 · Cited by 19 · see citing works
Vegliante, M. C., Mazzara, S., Zaccaria, G. M., Summa, S. D., Esposito, F., Melle, F., Motta, G., Sapienza, M. R., Opinto, G., Volpe, G., et al. (2022) · Hematological Oncology · doi:10.1002/hon.3050 · Cited by 19 · see citing works
Yuan, B., Shi, K., Zha, J., Cai, Y., Gu, Y., Huang, K., Yue, W., Zhai, Q., Ding, N., Ren, W., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-022-05545-7 · Cited by 20 · see citing works
A Potent In Vivo Antitumor Efficacy of Novel Recombinant Type I Interferon
Zhang, K.-J., Yin, X., Yang, Y., Li, H., Xu, Y., Chen, L.-Y., Liu, X.-J., Yuan, S., Fang, X.-L., Xiao, J., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1386 · Cited by 20 · see citing works
Srivastava, S., Widmann, S., Ho, C., Nguyen, D., Nguyen, A., Premaratne, A., Gustafsson, J.-Α., & Lin, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249622 · Cited by 20 · see citing works
Induction of pyroptosis in colon cancer cells by LXRβ
Rébé, C., Derangère, V., & Ghiringhelli, F. (2015) · Molecular & Cellular Oncology · doi:10.4161/23723548.2014.970094 · Cited by 21 · see citing works
- Authors
- Pencheva, N., Buss, C. G., Posada, J., Merghoub, T., & Tavazoie, S. F.
- Affiliations
- Rockefeller University (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Tavazoie, Sohail F.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 156
- Issue
- 5
- Pages
- 986-1001
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2133717967
- Cited by
- 175
- References
- 40
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 15 · 2023: 14 · 2022: 17 · 2021: 14 · 2020: 27 · 2019: 14 · 2018: 16 · 2017: 10 · 2016: 13 · 2015: 20 · 2014: 6
- FWCI
- 6.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- Rita Allen Foundation
- Melanoma Research Alliance
- Allen Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- metastatic melanoma, liver X receptor, apolipoprotein E, metastasis suppression, angiogenesis, brain metastases, CTLA-4 blockade, combination therapy, stromal cells, transcriptional activation
- MeSH terms
- Liver X Receptors, Benzenesulfonamides, Animals, Apolipoproteins E, Benzoates, Benzylamines, Cells, Cultured, Disease Models, Animal, Fluorocarbons, Humans, Hydrocarbons, Fluorinated, Melanoma, Neoplasm Metastasis, Skin Neoplasms, Sulfonamides, Transcription, Genetic, Signal Transduction, Mice, Orphan Nuclear Receptors
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