Axl is an essential epithelial-to-mesenchymal transition-induced regulator of breast cancer metastasis and patient survival
Open accessAbstract
Metastasis underlies the majority of cancer-related deaths. Thus, furthering our understanding of the molecular mechanisms that enable tumor cell dissemination is a vital health issue. Epithelial-to-mesenchymal transitions (EMTs) endow carcinoma cells with enhanced migratory and survival attributes that facilitate malignant progression. Characterization of EMT effectors is likely to yield new insights into metastasis and novel avenues for treatment. We show that the presence of the receptor tyrosine kinase Axl in primary breast cancers independently predicts strongly reduced overall patient survival, and that matched patient metastatic lesions show enhanced Axl expression. We demonstrate that Axl is strongly induced by EMT in immortalized mammary epithelial cells that establishes an autocrine signaling loop with its ligand, Gas6. Epiallelic RNA interference analysis in metastatic breast cancer cells delineated a distinct threshold of Axl expression for mesenchymal-like in vitro cell invasiveness and formation of tumors in foreign and tissue-engineered microenvironments in vivo. Importantly, in two different optical imaging-based experimental breast cancer models, Axl knockdown completely prevented the spread of highly metastatic breast carcinoma cells from the mammary gland to lymph nodes and several major organs and increased overall survival. These findings suggest that Axl represents a downstream effector of the tumor cell EMT that is required for breast cancer metastasis. Thus, the detection and targeted treatment of Axl-expressing tumors represents an important new therapeutic strategy for breast cancer.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A growing body of literature supports an essential role for AXL in promoting metastasis within many tumor types, including breast, ovarian, and lung.
“A growing body of literature supports an essential role for AXL in promoting metastasis within many tumor types, including breast (81), ovarian (82), and lung (83).”
From Hypoxic control of metastasis (2016) · cites this paper as [81]
Cites
The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Mani, S. A., Guo, W., Liao, M.-J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., Brooks, M. W., Reinhard, F., Zhang, C. C., Shipitsin, M. V., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.027 · Cited by 8,679 · see citing works
Epithelial–mesenchymal transitions in tumour progression
Thiery, J. P. (2002) · Nature reviews. Cancer · doi:10.1038/nrc822 · Cited by 6,632 · see citing works
Involvement of chemokine receptors in breast cancer metastasis
Müller, A., Homey, B., Soto, H., Ge, N., Catron, D., Buchanan, M. E., McClanahan, T., Murphy, E., Yuan, W., Wagner, S. N., et al. (2001) · Nature · doi:10.1038/35065016 · Cited by 5,340 · see citing works
Complex networks orchestrate epithelial–mesenchymal transitions
Thiery, J. P., & Sleeman, J. P. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1835 · Cited by 3,961 · see citing works
Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis
Yang, J., Mani, S. A., Donaher, J. L., Ramaswamy, S., Itzykson, R., Côme, C., Savagner, P., Gitelman, I., Richardson, A. L., & Weinberg, R. A. (2004) · Cell · doi:10.1016/j.cell.2004.06.006 · Cited by 3,856 · see citing works
Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits
Polyak, K., & Weinberg, R. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2620 · Cited by 3,302 · see citing works
A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes
Neve, R. M., Chin, K., Fridlyand, J., Yeh, J., Baehner, F. L., Fevr, T., Clark, L., Bayani, N., Coppé, J., Tong, F. K., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.10.008 · Cited by 3,191 · see citing works
Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype?
Peinado, H., Olmeda, D., & Cano, A. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2131 · Cited by 3,121 · see citing works
PETERSEN, O. W., Rønnov‐Jessen, L., Howlett, A. R., & Bissell, M. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.19.9064 · Cited by 1,096 · see citing works
Cancer Metastasis Is Accelerated through Immunosuppression during Snail-Induced EMT of Cancer Cells
Kudo‐Saito, C., Shirako, H., Takeuchi, T., & Kawakami, Y. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.01.023 · Cited by 872 · see citing works
Engineering tumors with 3D scaffolds
Fischbach, C., Chen, R., Matsumoto, T., Schmelzle, T., Brugge, J. S., Polverini, P. J., & Mooney, D. J. (2007) · Nature Methods · doi:10.1038/nmeth1085 · Cited by 823 · see citing works
Stabilization of Snail by NF-κB Is Required for Inflammation-Induced Cell Migration and Invasion
Wu, Y., Deng, J., Rychahou, P. G., Qiu, S., Evers, B. M., & Zhou, B. P. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.016 · Cited by 797 · see citing works
Linger, R. M. A., Keating, A. K., Earp, H. S., & Graham, D. K. (2008) · Advances in cancer research · doi:10.1016/s0065-230x(08)00002-x · Cited by 750 · see citing works
Epithelial-Mesenchymal Transition
Klymkowsky, M. W., & Savagner, P. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080545 · Cited by 561 · see citing works
Imagable 4T1 model for the study of late stage breast cancer
Tao, K. X., Fang, M., Alroy, J., & Sahagian, G. G. (2008) · BMC Cancer · doi:10.1186/1471-2407-8-228 · Cited by 525 · see citing works
Bone marrow cells in the ‘pre-metastatic niche’: within bone and beyond
Kaplan, R. N., Psaila, B., & Lyden, D. C. (2006) · Cancer and Metastasis Reviews · doi:10.1007/s10555-006-9036-9 · Cited by 335 · see citing works
Cancer cell angiogenic capability is regulated by 3D culture and integrin engagement
Fischbach, C., Kong, H. J., Hsiong, S. X., Evangelista, M. B., Yuen, W. W., & Mooney, D. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808932106 · Cited by 312 · see citing works
Mahadevan, D., Cooke, L. S., Riley, C., Swart, R. E., Simons, B. W., Croce, K. D., Wisner, L., Iorio, M. V., Shakalya, K., Garewal, H. S., et al. (2007) · Oncogene · doi:10.1038/sj.onc.1210173 · Cited by 283 · see citing works
Hutterer, M., Knyazev, P. G., Abate, A., Reschke, M., Maier, H., Stefanova, N., Knyazeva, T., Barbieri, V., Reindl, M., Muigg, A., et al. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0862 · Cited by 281 · see citing works
Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases
Hafizi, S., & Dahlbäck, B. (2006) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2006.04.004 · Cited by 261 · see citing works
Kenny, H. A., Krausz, T., Yamada, S. D., & Lengyel, E. (2007) · International Journal of Cancer · doi:10.1002/ijc.22874 · Cited by 243 · see citing works
Vajkoczy, P., Knyazev, P. G., Kunkel, A., Capelle, H., Behrndt, S., von Tengg‐Kobligk, H., Kiessling, F. M., Eichelsbacher, U., Essig, M., Read, T., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510923103 · Cited by 239 · see citing works
Phosphoproteomic analysis of Her2/neu signaling and inhibition
Bose, R., Molina, H., Patterson, A., Bitok, J. K., Periaswamy, B., Bader, J. S., Pandey, A., & Cole, P. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603948103 · Cited by 215 · see citing works
AXL Is a Potential Target for Therapeutic Intervention in Breast Cancer Progression
Zhang, Y., Knyazev, P. G., Cheburkin, Y. V., Sharma, K., Knyazev, Y. P., Őrfi, L., Szabadkai, I., Daub, H., Kéri, G., & Ullrich, A. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-2661 · Cited by 214 · see citing works
Koorstra, J.-B. M., Karikari, C. A., Feldmann, G., Bisht, S., Rojas, P. L., Offerhaus, G. J. A., Alvarez, H., & Maitra, A. (2009) · Cancer Biology & Therapy · doi:10.4161/cbt.8.7.7923 · Cited by 208 · see citing works
Multiple Roles for the Receptor Tyrosine Kinase Axl in Tumor Formation
Holland, S. J., Powell, M. J., Franci, C., Chan, E. W., Friera, A. M., Atchison, R. E., McLaughlin, J. R., Swift, S. E., Pali, E. S., Yam, G. C., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0993 · Cited by 201 · see citing works
Self-citationMechanisms of malignant progression
Weinberg, R. A. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn104 · Cited by 167 · see citing works
The Evolving Portrait of Cancer MetastasisPreprint
Gupta, P. B., Mani, S. A., YANG, J., Hartwell, K. A., & Weinberg, R. A. (2005) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2005.70.033 · Cited by 92 · see citing works
Wang, H., Kåresen, R., Hervik, A., & Thoresen, S. (2001) · Cancer Causes & Control · doi:10.1023/a:1008999403069 · Cited by 72 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Scenic: single-cell regulatory network inference and clustering.
Aibar, S., González-Blas, C. B., Moerman, T., Huynh-Thu, V. A., Imrichova, H., Hulselmans, G., Rambow, F., Marine, J.-C., Geurts, P., Aerts, J., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4463 · Cited by 6,520 · see citing works
Nieto, M. A., Huang, R. Y.-J., Jackson, R. A., & Thiery, J. P. (2016) · Cell · doi:10.1016/j.cell.2016.06.028 · Cited by 4,492 · see citing works
Visualization and analysis of gene expression in tissue sections by spatial transcriptomics
Ståhl, P. L., Salmén, F., Vickovic, S., Lundmark, A., Navarro, J. F., Magnusson, J., Giacomello, S., Asp, M., Westholm, J. O., Huss, M., et al. (2016) · Science · doi:10.1126/science.aaf2403 · Cited by 3,834 · see citing works
EMT, CSCs, and drug resistance: the mechanistic link and clinical implications
Shibue, T., & Weinberg, R. A. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.44 · Cited by 2,539 · see citing works
Rankin, E. B., & Giaccia, A. J. (2016) · Science · doi:10.1126/science.aaf4405 · Cited by 1,340 · see citing works
Byers, L. A., Diao, L., Wang, J., Saintigny, P., Girard, L., Peyton, M., Shen, L., Fan, Y., Giri, U., Tumula, P. K., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1558 · Cited by 1,059 · see citing works
Epithelial-Mesenchymal Transition in Cancer: A Historical Overview
Ribatti, D., Tamma, R., & Annese, T. (2020) · Translational Oncology · doi:10.1016/j.tranon.2020.100773 · Cited by 1,012 · see citing works
Epithelial-to-mesenchymal transition in cancer: complexity and opportunities
Zhang, Y., & Weinberg, R. A. (2018) · Frontiers of Medicine · doi:10.1007/s11684-018-0656-6 · Cited by 660 · see citing works
Cellular mechanotransduction in health and diseases: from molecular mechanism to therapeutic targets
Di, X., Gao, X., Peng, L., Ai, J., Jin, X., Qi, S., Li, H., Wang, K., & Luo, D. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01501-9 · Cited by 659 · see citing works
Vuoriluoto, K., Haugen, H., Kiviluoto, S., Mpindi, J.-P., Nevo, J., Gjerdrum, C., Tiron, C. E., Lorens, J. B., & Ivaska, J. (2010) · Oncogene · doi:10.1038/onc.2010.509 · Cited by 643 · see citing works
Self-citationLow MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma
Müller, J., Krijgsman, O., Tsoi, J., Robert, L., Hugo, W., Song, C., Kong, X., Possik, P. A., Cornelissen-Steijger, P. D. M., Foppen, M. H. G., et al. (2014) · Nature Communications · doi:10.1038/ncomms6712 · Cited by 639 · see citing works
Molecular analysis of circulating tumour cells—biology and biomarkers
Krebs, M., Metcalf, R. L., Carter, L., Brady, G., Blackhall, F. H., & Dive, C. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2013.253 · Cited by 620 · see citing works
Lemke, G. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009076 · Cited by 598 · see citing works
Holland, S. J., Pan, A., Franci, C., Hu, Y., Chang, B. Y., Li, W., Duan, M., Torneros, A., Yu, J., Heckrodt, T. J., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-2997 · Cited by 554 · see citing works
A microfluidic 3D in vitro model for specificity of breast cancer metastasis to bone
Bersini, S., Jeon, J. S., Dubini, G., Arrigoni, C., Chung, S., Charest, J. L., Moretti, M., & Kamm, R. D. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2013.11.050 · Cited by 534 · see citing works
Zhu, C., Wei, Y., & Wei, X. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1090-3 · Cited by 498 · see citing works
Sennino, B., Ishiguro‐Oonuma, T., Wei, Y., Naylor, R. M., Williamson, C. W., Bhagwandin, V. J., Tabruyn, S. P., You, W., Chapman, H. A., Christensen, J. G., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0240 · Cited by 404 · see citing works
Targeting EMT in cancer: opportunities for pharmacological intervention
Davis, F. M., Stewart, T. A., Thompson, E. W., & Monteith, G. R. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.06.006 · Cited by 361 · see citing works
Biddle, A., Liang, K. X., Gammon, L., Fazil, B., Harper, L. J., Emich, H., Costea, D. E., & Mackenzie, I. C. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1059 · Cited by 352 · see citing works
Epithelial–mesenchymal transition: a new target in anticancer drug discovery
Marcucci, F., Stassi, G., & Maria, R. D. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.13 · Cited by 340 · see citing works
Cancer stem cells: problems for therapy?
Alison, M. R., Lim, S. M. L., & Nicholson, L. J. (2010) · The Journal of Pathology · doi:10.1002/path.2793 · Cited by 312 · see citing works
ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types
Lehmann, W., Mossmann, D., Kleemann, J., Mock, K., Meisinger, C., Brummer, T., Herr, R., Brabletz, S., Stemmler, M. P., & Brabletz, T. (2016) · Nature Communications · doi:10.1038/ncomms10498 · Cited by 305 · see citing works
Asiedu, M. K., Beauchamp‐Perez, F., Ingle, J. N., Behrens, M. D., Radisky, D. C., & Knutson, K. L. (2013) · Oncogene · doi:10.1038/onc.2013.57 · Cited by 302 · see citing works
Blick, T., Hugo, H. J., Widodo, E., Waltham, M. C., Pinto, C., Mani, S. A., Weinberg, R. A., Neve, R. M., Lenburg, M. E., & Thompson, E. W. (2010) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-010-9175-z · Cited by 291 · see citing works
Meyer, A. S., Miller, M. A., Gertler, F. B., & Lauffenburger, D. A. (2013) · Science Signaling · doi:10.1126/scisignal.2004155 · Cited by 283 · see citing works
Emerging role of tumor cell plasticity in modifying therapeutic response
Qin, S., Jiang, J., Lü, Y., Nice, E. C., Huang, C., Zhang, J., & He, W. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00313-5 · Cited by 274 · see citing works
Controlling escape from angiogenesis inhibitors
Sennino, B., & McDonald, D. M. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3366 · Cited by 265 · see citing works
VEGF and c-Met Blockade Amplify Angiogenesis Inhibition in Pancreatic Islet Cancer
You, W., Sennino, B., Williamson, C. W., Falcón, B. L., Hashizume, H., Yao, L., Aftab, D. T., & McDonald, D. M. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2527 · Cited by 262 · see citing works
Bypass Mechanisms of Resistance to Receptor Tyrosine Kinase Inhibition in Lung Cancer
Niederst, M. J., & Engelman, J. A. (2013) · Science Signaling · doi:10.1126/scisignal.2004652 · Cited by 261 · see citing works
Martín, Y. D. P., Park, D., Ramachandran, A., Ombrato, L., Calvo, F., Chakravarty, P., Spencer‐Dene, B., Derzsi, S., Hill, C. S., Sahai, E. A., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.11.025 · Cited by 246 · see citing works
Lal, A., Thomas, M. P., Altschuler, G. M., Navarro, F., O’Day, E. M., Li, X. L., Concepcion, C. P., Han, Y.-C., Thiery, J., Rajani, D. K., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002363 · Cited by 245 · see citing works
Ye, X., Li, Y., Stawicki, S. S., Couto, S. S., Eastham‐Anderson, J., Kallop, D. Y., Weimer, R. M., Wu, Y., & Pei, L. (2010) · Oncogene · doi:10.1038/onc.2010.268 · Cited by 231 · see citing works
AXL Is an Essential Factor and Therapeutic Target for Metastatic Ovarian Cancer
Rankin, E. B., Fuh, K. C., Taylor, T. E., Krieg, A. J., Musser, M., Yuan, J., Wei, K., Kuo, C. J., Longacre, T. A., & Giaccia, A. J. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1267 · Cited by 229 · see citing works
Targeting Axl and Mer Kinases in Cancer
Verma, A. R., Warner, S. L., Vankayalapati, H., Bearss, D. J., & Sharma, S. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0116 · Cited by 226 · see citing works
Cancer stem cells: In the line of fire
Alison, M. R., Lin, W., Lim, S. M. L., & Nicholson, L. J. (2012) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2012.03.003 · Cited by 222 · see citing works
Linger, R. M. A., Cohen, R. A., Cummings, C. T., Sather, S., Migdall-Wilson, J., Middleton, D., Lu, X.-J., Barón, A. E., Franklin, W. A., Merrick, D., et al. (2012) · Oncogene · doi:10.1038/onc.2012.355 · Cited by 220 · see citing works
Jiang, N., Wang, X., Xie, X., Liao, Y., Liu, N., Liu, J., Miao, N., Shen, J., & Peng, T. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.06.009 · Cited by 212 · see citing works
A systems view of epithelial–mesenchymal transition signaling states
Thomson, S., Petti, F., Sujka-Kwok, I., Mercado, P., Bean, J. M., Monaghan, M., Seymour, S. L., Argast, G. M., Epstein, D. M., & Haley, J. D. (2010) · Clinical & Experimental Metastasis · doi:10.1007/s10585-010-9367-3 · Cited by 210 · see citing works
AXL Inhibitors in Cancer: A Medicinal Chemistry Perspective
Myers, S. H., Brunton, V. G., & Unciti‐Broceta, A. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01273 · Cited by 210 · see citing works
EMT: A mechanism for escape from EGFR-targeted therapy in lung cancer
Tulchinsky, E. M., Demidov, O. N., Kriajevska, M. V., Barlev, N. A., & Имянитов, Е. Н. (2018) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2018.10.003 · Cited by 209 · see citing works
New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma
Wang, T., & Zhang, K.-H. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01316 · Cited by 195 · see citing works
AXL kinase as a novel target for cancer therapy
Wu, X., Liu, X., Koul, S., Lee, C. Y., Zhang, Z., & Halmos, B. (2014) · Oncotarget · doi:10.18632/oncotarget.2542 · Cited by 191 · see citing works
Axl as a mediator of cellular growth and survival
Axelrod, H. D., & Pienta, K. J. (2014) · Oncotarget · doi:10.18632/oncotarget.2422 · Cited by 190 · see citing works
AXL-Driven EMT State as a Targetable Conduit in Cancer
Antony, J., & Huang, R. Y. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0392 · Cited by 182 · see citing works
Targeting Gas6/TAM in cancer cells and tumor microenvironment
Wu, G., Ma, Z., Cheng, Y., Hu, W., Deng, C., Jiang, S., Li, T. X., Chen, F., & Yang, Y. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0769-1 · Cited by 180 · see citing works
Nilsson, M. B., Sun, H., Robichaux, J., Pfeifer, M., McDermott, U., Travers, J., Diao, L., Xi, Y., Tong, P., Shen, L., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaz4589 · Cited by 177 · see citing works
The Receptor Tyrosine Kinase AXL in Cancer Progression
Rankin, E. B., & Giaccia, A. J. (2016) · Cancers · doi:10.3390/cancers8110103 · Cited by 170 · see citing works
Evans, K. W., Yuca, E., Scott, S. M., Zhao, M., Arango, N. P., Pico, C. X. C., Saridogan, T., Shariati, M., Class, C. A., Bristow, C. A., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-20-3242 · Cited by 168 · see citing works
Taking aim at Mer and Axl receptor tyrosine kinases as novel therapeutic targets in solid tumors
Linger, R. M. A., Keating, A. K., Earp, H. S., & Graham, D. K. (2010) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2010.515980 · Cited by 167 · see citing works
Cancer stem cells and EMT in carcinoma
Biddle, A., & Mackenzie, I. C. (2012) · Cancer and Metastasis Reviews · doi:10.1007/s10555-012-9345-0 · Cited by 167 · see citing works
Breast cancer stem cells: Multiple capacities in tumor metastasis
Geng, S., Alexandrou, A. T., & Li, J. J. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.03.036 · Cited by 167 · see citing works
Targeted therapy and drug resistance in triple-negative breast cancer: the EGFR axis
Lev, S. (2020) · Biochemical Society Transactions · doi:10.1042/bst20191055 · Cited by 166 · see citing works
Wang, H., Zhang, H., Tang, L., Chen, H., Wu, C., Zhao, M., Yang, Y., Chen, X., & Liu, G. (2012) · Toxicology · doi:10.1016/j.tox.2012.09.017 · Cited by 164 · see citing works
Vimentin as a poor prognostic factor for triple-negative breast cancer
Yamashita, N., Tokunaga, E., Kitao, H., Hisamatsu, Y., Taketani, K., Akiyoshi, S., Okada, S., Aishima, S., Morita, M., & Maehara, Y. (2013) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-013-1376-6 · Cited by 161 · see citing works
The Difficulty of Targeting Cancer Stem Cell Niches
LaBarge, M. A. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-2933 · Cited by 153 · see citing works
Saleh, S. A., Al‐Mulla, F., & Luqmani, Y. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020610 · Cited by 159 · see citing works
Ludwig, K. F., Du, W., Sorrelle, N. B., Wnuk-Lipińska, K., Topalovski, M., Toombs, J. E., Cruz, V. H., Yabuuchi, S., Rajeshkumar, N. V., Maitra, A., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-1973 · Cited by 159 · see citing works
Self-citationAxl activates autocrine transforming growth factor‐β signaling in hepatocellular carcinoma
Reichl, P., Dengler, M., van Zijl, F., Huber, H., Führlinger, G., Reichel, C., Sieghart, W., Peck‐Radosavljevic, M., Grubinger, M., & Mikulits, W. (2014) · Hepatology · doi:10.1002/hep.27492 · Cited by 157 · see citing works
Ivaska, J. (2011) · Small GTPases · doi:10.4161/sgtp.2.1.15114 · Cited by 157 · see citing works
Axl-dependent signalling: a clinical update
Korshunov, V. A. (2011) · Clinical Science · doi:10.1042/cs20110411 · Cited by 156 · see citing works
The role of phosphatidylserine recognition receptors in multiple biological functions
Naeini, M. B., Bianconi, V., Pirro, M., & Sahebkar, A. (2020) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-020-00214-z · Cited by 156 · see citing works
Song, X., Wang, H., Logsdon, C. D., Rashid, A., Fleming, J. B., Abbruzzese, J. L., Gomez, H. F., Evans, D. B., & Wang, H. (2010) · Cancer · doi:10.1002/cncr.25483 · Cited by 155 · see citing works
Giles, K. M., Kalinowski, F. C., Candy, P. A., Epis, M. R., Zhang, P. M., Redfern, A. D., Stuart, L. M., Goodall, G. J., & Leedman, P. J. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0170 · Cited by 155 · see citing works
Targeting Axl With an High-affinity Inhibitory Aptamer
Cerchia, L., Esposito, C. L., Camorani, S., Rienzo, A., Stasio, L., Insabato, L., Affuso, A., & de Franciscis, V. (2012) · Molecular Therapy · doi:10.1038/mt.2012.163 · Cited by 153 · see citing works
Bárcena, C., Stefanović, M., Tutusaus, A., Joannas, L. D., Menéndez, A., García‐Ruiz, C., Sancho‐Bru, P., Marı́, M., Caballería, J., Rothlin, C. V., et al. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.04.013 · Cited by 151 · see citing works
AXL Inhibition Sensitizes Mesenchymal Cancer Cells to Antimitotic Drugs
Wilson, C., Ye, X., Pham, T., Lin, E., Chan, S., McNamara, E., Neve, R. M., Belmont, L., Koeppen, H., Yauch, R. L., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-1009 · Cited by 150 · see citing works
Kirane, A., Ludwig, K. F., Sorrelle, N. B., Haaland, G. S., Sandal, T., Ranaweera, R., Toombs, J. E., Wang, M., Dineen, S. P., Micklem, D., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2887-t · Cited by 150 · see citing works
Self-citationWang, C., Jin, H., Wang, N., Fan, S., Wang, Y., Zhang, Y., Lin, W., Tao, X., Gu, D., Zhao, F., et al. (2016) · Theranostics · doi:10.7150/thno.15083 · Cited by 149 · see citing works
The receptor tyrosine kinase Axl in cancer: Biological functions and therapeutic implications
Paccez, J. D., Vogelsang, M., Parker, M. I., & Zerbini, L. F. (2013) · International Journal of Cancer · doi:10.1002/ijc.28246 · Cited by 148 · see citing works
Reed, I. K. G., Phoenix, K. N., Hong, X., Tirnauer, J. S., Claffey, K. P., & White, B. A. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1534-y · Cited by 148 · see citing works
Sensi, M., Catani, M., Castellano, G., Nicolini, G., Alciato, F., Tragni, G., Santis, G. D., Bersani, I., Avanzi, G., Tomassetti, A., et al. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.218 · Cited by 148 · see citing works
Goyette, M.-A., Duhamel, S., Aubert, L., Pelletier, A., Savage, P., Thibault, M.-P., Johnson, R. M., Carmeliet, P., Basik, M., Gaboury, L. A., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.019 · Cited by 144 · see citing works
Gas6/Axl Signaling Pathway in the Tumor Immune Microenvironment
Tanaka, M., & Siemann, D. W. (2020) · Cancers · doi:10.3390/cancers12071850 · Cited by 144 · see citing works
An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis
Kariolis, M. S., Miao, Y. R., Jones, D. S., Kapur, S., Mathews, I. I., Giaccia, A. J., & Cochran, J. R. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1636 · Cited by 143 · see citing works
Bone-on-a-chip: Microfluidic technologies and microphysiologic models of bone tissue
Mansoorifar, A., Gordon, R., Bergan, R. C., & Bertassoni, L. E. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202006796 · Cited by 142 · see citing works
Paccez, J. D., Vasques, G. J., Correa, R. G., de Vasconcellos, J. F., Duncan, K., Gu, X., Bhasin, M., Libermann, T. A., & Zerbini, L. F. (2012) · Oncogene · doi:10.1038/onc.2012.89 · Cited by 141 · see citing works
The Epithelial-to-Mesenchymal Transition in Breast Cancer: Focus on Basal-Like Carcinomas
Fedele, M., Cerchia, L., & Chiappetta, G. (2017) · Cancers · doi:10.3390/cancers9100134 · Cited by 141 · see citing works
Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT–tamoxifen hybrid therapy
Theodossiou, T. A., Ali, M., Grigalavicius, M., Grallert, B., Dillard, P., Schink, K. O., Olsen, C. E., Wälchli, S., Inderberg, E. M., Kubin, A., et al. (2019) · npj Breast Cancer · doi:10.1038/s41523-019-0108-8 · Cited by 141 · see citing works
Choufani, S., Shapiro, J. S., Susiarjo, M., Butcher, D. T., Grafodatskaya, D., Lou, Y., Ferreira, J. C., Pinto, D., Scherer, S. W., Shaffer, L. G., et al. (2011) · Genome Research · doi:10.1101/gr.111922.110 · Cited by 139 · see citing works
Biddle, A., Gammon, L., Liang, K. X., Costea, D. E., & Mackenzie, I. C. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.01.007 · Cited by 134 · see citing works
Key Roles of AXL and MER Receptor Tyrosine Kinases in Resistance to Multiple Anticancer Therapies
Schoumacher, M., & Burbridge, M. F. (2017) · Current Oncology Reports · doi:10.1007/s11912-017-0579-4 · Cited by 132 · see citing works
LAMC2 enhances the metastatic potential of lung adenocarcinoma
Moon, Y. W., Rao, G., Kim, J., Shim, H. S., Park, K.-S., An, S. S., Kim, B. J., Steeg, P. S., Sarfaraz, S., Lee, L. C., et al. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2014.228 · Cited by 130 · see citing works
Kasikara, C., Kumar, S., Kimani, S. G., Tsou, W., Geng, K., Davra, V., Sriram, G., Devoe, C., Nguyen, K.-Q. N., Lewis-Antes, A., et al. (2017) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-16-0350 · Cited by 129 · see citing works
MiRNA-mediated EMT and CSCs in cancer chemoresistance
Dong, B., Li, S., Zhu, S., Yi, M., Luo, S., & Wu, K. (2021) · Experimental Hematology and Oncology · doi:10.1186/s40164-021-00206-5 · Cited by 127 · see citing works
Self-citationOkura, N., Nishioka, N., Yamada, T., Taniguchi, H., Tanimura, K., Katayama, Y., Yoshimura, A., Watanabe, S., Kikuchi, T., Shiotsu, S., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2321 · Cited by 120 · see citing works
Debruyne, D. N., Bhatnagar, N., Sharma, B., Luther, W., Moore, N. F., Cheung, N., Gray, N. S., & George, R. E. (2015) · Oncogene · doi:10.1038/onc.2015.434 · Cited by 119 · see citing works
Bagnyukova, T., Serebriiskii, I. G., Zhou, Y., Hopper-Borge, E. A., Golemis, E. A., & Astsaturov, I. A. (2010) · Cancer Biology & Therapy · doi:10.4161/cbt.10.9.13738 · Cited by 118 · see citing works
Antony, J., Tan, T. Z., Kelly, Z. L., Low, J. J. H., Choolani, M. A., Recchi, C., Gabra, H., Thiery, J. P., & Huang, R. Y. (2016) · Science Signaling · doi:10.1126/scisignal.aaf8175 · Cited by 118 · see citing works
Lequeux, A., Noman, M. Z., Xiao, M., Sauvage, D., Van Moer, K., Viry, E., Bocci, I., Hasmim, M., Bosseler, M., Berchem, G., et al. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.05.021 · Cited by 117 · see citing works
Molecular insights of Gas6/TAM in cancer development and therapy
Wu, G., Ma, Z., Hu, W., Wang, D., Gong, B., Fan, C., Jiang, S., Li, T. X., Gao, J., & Yang, Y. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.113 · Cited by 117 · see citing works
Low expression of long noncoding RNA GAS6-AS1 predicts a poor prognosis in patients with NSCLC
Han, L., Kong, R., Yin, D., Zhang, E., Xu, T., De, W., & Shu, Y. (2013) · Medical Oncology · doi:10.1007/s12032-013-0694-5 · Cited by 115 · see citing works
Dunne, P. D., McArt, D. G., Blayney, J. K., Kalimutho, M., Greer, S., Wang, T., Srivastava, S., Ong, C. W., Arthur, K., Loughrey, M. B., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1354 · Cited by 113 · see citing works
Mackiewicz, M., Huppi, K. E., Pitt, J. J., Dorsey, T. H., Ambs, S., & Caplen, N. J. (2011) · Breast Cancer Research and Treatment · doi:10.1007/s10549-011-1690-0 · Cited by 113 · see citing works
Hypoxia Stabilizes GAS6/Axl Signaling in Metastatic Prostate Cancer
Mishra, A., Wang, J., Shiozawa, Y., McGee, S., Kim, J., Jung, Y., Joseph, J., Berry, J. E., Havens, A. M., Pienta, K. J., et al. (2012) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-11-0569 · Cited by 112 · see citing works
Leconet, W., Chentouf, M., du Manoir, S., Chevalier, C., Sirvent, A., Aït-Arsa, I., Busson, M., Jarlier, M., Radosevic‐Robin, N., Theillet, C. G., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1316 · Cited by 109 · see citing works
Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies
Kariolis, M. S., Miao, Y. R., Diep, A. N., Nash, S. E., Olcina, M. M., Jiang, D., Jones, D. S., Kapur, S., Mathews, I. I., Koong, A. C., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85610 · Cited by 108 · see citing works
Chen, C., Zimmermann, M., Tinhofer, I., Kaufmann, A. M., & Albers, A. E. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.06.013 · Cited by 107 · see citing works
Leconet, W., Larbouret, C., Chardès, T., Thomas, G., Neiveyans, M., Busson, M., Jarlier, M., Radosevic‐Robin, N., Pugnière, M., Bernex, F., et al. (2013) · Oncogene · doi:10.1038/onc.2013.487 · Cited by 107 · see citing works
Vouri, M., Croucher, D. R., Kennedy, S. P., An, Q., Pilkington, G. J., & Hafizi, S. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.66 · Cited by 106 · see citing works
First Axl inhibitor enters clinical trials
Sheridan, C. (2013) · Nature Biotechnology · doi:10.1038/nbt0913-775a · Cited by 104 · see citing works
- Authors
- Gjerdrum, C., Tiron, C., Høiby, T., Stefansson, I., Haugen, H., Sandal, T., Collett, K., Li, S., McCormack, E., Gjertsen, B. T., Micklem, D. R., Akslen, L. A., Glackin, C., & Lorens, J. B.
- Affiliations
- Department of Biomedicine
- The Gade Institute, Pathology Section
- Beckman Research Institute (US)
- Haukeland University Hospital (NO)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-12-28
- Volume
- 107
- Issue
- 3
- Pages
- 1124-1129
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2824310
- OpenAlex
- W2003445065
- Cited by
- 594
- References
- 29
- Citations by year
- 2026: 14 · 2025: 30 · 2024: 21 · 2023: 44 · 2022: 34 · 2021: 37 · 2020: 55 · 2019: 39 · 2018: 37 · 2017: 45 · 2016: 52 · 2015: 42 · 2014: 40 · 2013: 29 · 2012: 27
- FWCI
- 12.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Helse Vest
- Universitetet i Bergen
- Norges Forskningsråd
- National Institutes of Health
- National Cancer Institute (R21CA107245, CA107245)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- AXL, epithelial-mesenchymal transition, breast cancer metastasis, Gas6, autocrine signaling, patient survival, tumor invasion, lymph node metastasis, therapeutic target, mammary epithelial cells
- MeSH terms
- Axl Receptor Tyrosine Kinase, Animals, Breast Neoplasms, Epithelial Cells, Female, Humans, Mesoderm, Neoplasm Invasiveness, Neoplasm Metastasis, Prognosis, Proto-Oncogene Proteins, Oncogene Proteins, Survival Analysis, Mice, SCID, Mice, Inbred NOD, Receptor Protein-Tyrosine Kinases, Tissue Engineering, RNA Interference, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review