Constitutively active Stat3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of Cten
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Abstract
The transcription factor signal transducer and activator of transcription 3 (STAT3) is constitutively activated in tumors of different origin, but the molecular bases for STAT3 requirement are only partly understood. To evaluate the contribution of enhanced Stat3 activation in a controlled model system, we generated knock-in mice wherein a mutant constitutively active Stat3C allele replaces the endogenous wild-type allele. Stat3C could enhance the tumorigenic power of the rat Neu oncogene in mouse mammary tumor virus (MMTV)-Neu transgenic mice, triggering the production of earlier onset, more invasive mammary tumors. Tumor-derived cell lines displayed higher migration, invasion, and metastatic ability and showed disrupted distribution of cell-cell junction markers mediated by Stat3-dependent overexpression of the COOH terminal tensin-like (Cten) focal adhesion protein, which was also significantly upregulated in Stat3C mammary tumors. Importantly, the proinflammatory cytokine interleukin-6 could mediate Cten induction in MCF10 cells in an exquisitely Stat3-dependent way, showing that Cten upregulation is a feature of inflammation-activated Stat3. In light of the emerging pivotal role of Stat3 in connecting inflammation and cancer, our identification of Cten as a Stat3-dependent mediator of migration provides important new insights into the oncogenic role of Stat3, particularly in the breast.
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The IL-6-STAT3 pathway is involved in the epithelial-mesenchymal transition, tumor migration, cancer stemness and the induction of HIF-1α and VEGF, two key players for angiogenesis.
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From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [133]
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BackgroundSTAT signaling in mammary gland differentiation, cell survival and tumorigenesis
Haricharan, S., & Li, Y. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.03.014 · Cited by 130 · see citing works
“For instance, MMTV-Neu transgenic mice with a constitutively active STAT3 allele develop significantly more aggressive and metastatic tumors than those without (Barbieri et al., 2010).”
BackgroundZhang, J.-L., Xiao, Z., Lai, D., Sun, J., He, C., Chu, Z., Ye, H., Chen, S.-F., & Wang, J. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.251 · Cited by 125 · see citing works
“In fact, the activation of STAT3 has been widely implicated in the proliferation, migration and invasion of different cancer cells (Bollrath and Greten, 2009; Barbieri et al , 2010; Chiu et al , 2011; Fukuda et al , 2011).”
RetractedAnti-angiogenic and anti-metastatic activity of JAK inhibitor AZD1480
Xin, H., Herrmann, A., Reckamp, K., Zhang, W., Pal, S., Hedvat, M., Zhang, C.-Y., Liang, W., Scuto, A., Weng, S., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-1217 · Cited by 112 · see citing works
“AZD1480 inhibits lung metastasis and factors important for premetastatic niche formation STAT3 has been implicated in tumor migration and metastasis (9, 23, 24).”
Deshmukh, S., Srivastava, S., Bhardwaj, A., Singh, A., Tyagi, N., Marimuthu, S., Dyess, D., Zotto, V. D. D., Carter, J., & Singh, S. (2015) · OncoTarget · doi:10.18632/oncotarget.3591 · Cited by 111 · see citing works
Barrueco, R. R., Yu, J., Saucedo-Cuevas, L. P., Oliván, M., Llobet‐Navàs, D., Putcha, P., Castro, V., Murga-Penas, E., Collazo-Lorduy, A., Castillo-Martín, M., et al. (2015) · Genes & Development · doi:10.1101/gad.262642.115 · Cited by 108 · see citing works
“Activation of STAT3 in metastatic progression is well established and has been associated with myeloid cell recruitment (Chang et al. 2013), angiogenesis (Chang et al. 2013), epithelial–mesenchymal transition (Wendt et al. 2014), and migration (Barbieri et al. 2010a).”
BackgroundTargeting the tumor microenvironment
Bournazou, E., & Bromberg, J. (2013) · JAK-STAT · doi:10.4161/jkst.23828 · Cited by 191 · see citing works
Snyder, M., Huang, X., & Zhang, J. J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.286245 · Cited by 99 · see citing works
Cytokine disbalance in common human cancers.
Culig, Z. (2011) · Biochimica et Biophysica Acta · doi:10.1016/j.bbamcr.2010.12.010 · Cited by 98 · see citing works
Cellular and molecular effects of the mTOR inhibitor everolimus
Saran, U., Foti, M., & Dufour, J. (2015) · Clinical Science · doi:10.1042/cs20150149 · Cited by 106 · see citing works
Wang, Y., Wu, C., Zhang, C., Li, Z., Zhu, T., Chen, J., Ren, Y. T., Wang, X., Zhang, L., & Zhou, X. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.08.009 · Cited by 94 · see citing works
Wu, L.-Y., Du, H., Li, Y., Qu, P., & Yan, C. (2011) · American Journal of Pathology · doi:10.1016/j.ajpath.2011.06.028 · Cited by 95 · see citing works
Kim, E.-S., Kim, J.-S., Kim, S. G., Hwang, S., Lee, C. H., & Moon, A. (2011) · Journal of Cell Science · doi:10.1242/jcs.076794 · Cited by 93 · see citing works
“Invasion, migration and metastasis of breast cancer cells are mediated through NFkB and cytokines such as interleukin 6 (Wu et al., 2009; Barbieri et al., 2010).”
BackgroundLee, H. H., Jung, J., Moon, A., Kang, H., & Cho, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133143 · Cited by 88 · see citing works
“The enhanced expression of STAT3 is manifested in ER-negative breast cancers [15] and closely related to the invasiveness and metastasis of cancer cells [16,17].”
BackgroundRigiracciolo, D. C., Santolla, M. F., Lappano, R., Vivacqua, A., Cirillo, F., Galli, G. R., Talia, M., Muglia, L., PELLEGRINO, M. A., Nohata, N., et al. (2019) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-019-1056-8 · Cited by 94 · see citing works
Avalle, L., Raggi, L., Monteleone, E., Savino, A., Viavattene, D., Statello, L., Camperi, A., Stabile, S. A., Salemme, V., Marzo, N. D., et al. (2022) · Oncogene · doi:10.1038/s41388-021-02172-y · Cited by 108 · see citing works
“RESULTS STAT3 is required for in vitro pro-tumorigenic functions of primary CAFs CAFs were derived from NeuT transgenic mammary tumors [18] and analyzed for the expression of typical CAF markers along with normal and mouse embryonal fibroblasts (NFs, MEFs) (Supplementary Fig 1).”
BackgroundSelf-citationTcf3 promotes cell migration and wound repair through regulation of lipocalin 2
Miao, Q., Ku, A., Nishino, Y., Howard, J. M., Rao, A., Shaver, T., Garcia, G. E., Le, D., Karlin, K. L., Westbrook, T. F., et al. (2014) · Nature Communications · doi:10.1038/ncomms5088 · Cited by 74 · see citing works
Self-citationMartínez‐Fábregas, J., Prescott, A. R., van Kasteren, S. I., Pedrioli, D. M. L., McLean, W. H. I., Moles, A., Reinheckel, T., Poli, V., & Watts, C. K. W. (2018) · Nature Communications · doi:10.1038/s41467-018-07741-6 · Cited by 81 · see citing works
Self-citationSTAT3 isoforms: Alternative fates in cancer?
Aigner, P., Just, V., & Stoiber, D. (2018) · Cytokine · doi:10.1016/j.cyto.2018.07.014 · Cited by 80 · see citing works
The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer
Hughes, K., & Watson, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061695 · Cited by 69 · see citing works
“Similarly, mice harbouring a constitutively active STAT3 allele (STAT3C) in a transgenic MMTV-Neu (ErbB2) background, exhibited more invasive mammary tumours with earlier onset than those with wild-type STAT3 alleles [77].”
BackgroundSelf-citationZhang, G., Guo, L., Yang, C., Liu, Y., He, Y., Du, Y., Wang, W., & Gao, F. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1172154 · Cited by 81 · see citing works
Impacts of micro and nanoplastics on human health
Jayavel, S., Govindaraju, B., Michael, J., & Viswanathan, B. (2024) · Bulletin of the National Research Centre · doi:10.1186/s42269-024-01268-1 · Cited by 67 · see citing works
“Human breast cancer cells were infected by PPMPs with irregular forms; in particular, exposure to PPMPs enhanced the expression of genes related to the cell cycle and the release of IL-6 from MDA-MB-231 and MCF7 cells (Barbieri et al. 2010; Carpenter and Lo 2014).”
BackgroundTherapeutic Implication of SOCS1 Modulation in the Treatment of Autoimmunity and Cancer
Sharma, J., & Larkin, J. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00324 · Cited by 75 · see citing works
Venturutti, L., Romero, L., Urtreger, A., Chervo, M., Russo, R., Mercogliano, M., Inurrigarro, G., Pereyra, M., Proietti, C., Izzo, F., et al. (2016) · Oncogene · doi:10.1038/onc.2015.281 · Cited by 65 · see citing works
STAT3 can serve as a hit in the process of malignant transformation of primary cells
Demaria, M., Misale, S., Giorgi, C., Miano, V., Camporeale, A., Campisi, J., Pinton, P., & Poli, V. (2012) · Cell Death and Differentiation · doi:10.1038/cdd.2012.20 · Cited by 59 · see citing works
“continuous, weak STAT3 activation, we have recently generated knock-in mice expressing physiological levels of the constitutively active STAT3C mutant form.(13) We have shown that constitutively active STAT3 acts as a master”
BackgroundSelf-citationCten signals through integrin-linked kinase (ILK) and may promote metastasis in colorectal cancer
Albasri, A., Al-ghamdi, S., Fadhil, W., Aleskandarany, M., Liao, Y.-C., Jackson, D., Лобо, Д., Lo, S.-H., Kumari, R., Durrant, L., et al. (2011) · Oncogene · doi:10.1038/onc.2011.26 · Cited by 64
“As Cten is a recently described gene, data about its downstream targets are sparse, although recent studies suggest that Cten signalling occurs through the Stat3 pathway (Barbieri et al., 2010).”
BackgroundThe two faces of Janus kinases and their respective STATs in mammary gland development and cancer
Wagner, K., & Schmidt, J. W. (2011) · Journal of Carcinogenesis · doi:10.4103/1477-3163.90677 · Cited by 55 · see citing works
“[83,84] A recent report by Barbieri and colleagues shows that the constitutive activation of Stat3 results in accelerated mammary tumorigenesis and an increase in the metastatic potential of ErbB2 expressing cancer cells.[85] In contrast, a knockout of Stat3 prior to tumorigenesis shows that this signal transducer is…”
BackgroundThe Role of Inflammation in Inflammatory Breast Cancer
Fouad, T. M., Kogawa, T., Reuben, J. M., & Ueno, N. T. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-3-0348-0837-8_3 · Cited by 67 · see citing works
“Additionally, constitutive activation of STAT led to accelerated mammary tumorigenesis and increased metastatic potential in cancer cells expressing ErbB2 (Barbieri et al. 2010).”
BackgroundAdipocytokines and breast cancer
Li, J., & Han, X. (2018) · Current Problems in Cancer · doi:10.1016/j.currproblcancer.2018.01.004 · Cited by 61 · see citing works
Implications of stemness-related signaling pathways in breast cancer response to therapy.
Angeloni, V., Tiberio, P., Appierto, V., & Daidone, M. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2014.08.004 · Cited by 60 · see citing works
Wright, K. L., Adams, J. R., Liu, J. C., Loch, A. J., Wong, R. G., Jo, C. E. B., Beck, L. A., Santhanam, D., Weiss, L., Mei, X., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2992 · Cited by 59 · see citing works
“Given the published link between Stat3 and metastasis (18, 19), we also screened tumor bearing mice from Pik3ca;Stat3 transgenics for disseminated disease.”
BackgroundThe Stat3 paradox: A killer and an oncogene
Resemann, H. K., Watson, C. J., & Lloyd‐Lewis, B. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.06.029 · Cited by 58 · see citing works
Self-citationZhou, G., Yi, Y., Jin, L., Lin, W., Fang, P., Lin, X.-Z., Zheng, Y., & Pan, C. (2016) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.04.013 · Cited by 59 · see citing works
Snyder, M., Huang, J., Huang, X.-Y., & Zhang, J. J. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.591719 · Cited by 57 · see citing works
“In breast cancer, increased levels of IL-6 and activated Stat3 promote not only tumor growth but also metastasis (7, 16, 17).”
BackgroundErbB-2 nuclear function in breast cancer growth, metastasis and resistance to therapy.
Elizalde, P., Russo, R. C., Chervo, M. F., & Schillaci, R. (2016) · Endocrine-Related Cancer · doi:10.1530/erc-16-0360 · Cited by 54 · see citing works
Lung Tumor-Associated Dendritic Cell-Derived Amphiregulin Increased Cancer Progression
Hsu, Y.-L., Huang, M.-S., Cheng, D.-E., Hung, J., Yang, C.-J., Chou, S., & Kuo, P. (2011) · Journal of Immunology · doi:10.4049/jimmunol.1100996 · Cited by 51 · see citing works
“STAT3 is activated by multiple receptor and nonreceptor tyrosine kinases in response to various cytokines, hormones, and growth factors, and abnormal activation of STAT3 signaling has been seen in multiple tumors (28, 29).”
BackgroundCten Is Targeted by Kras Signalling to Regulate Cell Motility in the Colon and Pancreas
Alghamdi, S. A. A., Albasri, A. M., Cachat, J., Ibrahem, S., Muhammad, B. A., Jackson, D., Nateri, A. S., Kindle, K. B., & Ilyas, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020919 · Cited by 44 · see citing works
“Recently Stat3 has been reported as a modulator of Cten expression [21] and may represent an alternate pathway for Cten regulation.”
BackgroundCamporeale, A., Marino, F., Papageorgiou, A., Carai, P., Fornero, S., Fletcher, S., Page, B., Gunning, P., Forni, M., Chiarle, R., et al. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201201876 · Cited by 48 · see citing works
“Knock-in mice where the wild type (WT) STAT3 allele was replaced by its constitutively active artificial mutant form, STAT3C, were recently generated in our laboratory.”
InfluentialSelf-citationSonnenblick, A., Shriki, A., Galun, E., Axelrod, J., Daum, H., Rottenberg, Y., Hamburger, T., Mali, B., & Peretz, T. (2012) · Clinical and Translational Oncology · doi:10.1007/s12094-012-0789-z · Cited by 48 · see citing works
“Indeed, preclinical experiments in murine models demonstrated that STAT3 is required for migration and metastasis in mammary tumours [15, 16].”
BackgroundExpression and clinical significance of STAT3, P-STAT3, and VEGF-C in small cell lung cancer.
Zhao, X., Sun, X., & Li, X.-L. (2012) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2012.13.6.2873 · Cited by 46
“regulates genes related to cell proliferation, metastasis, and survival time (Garcia et al., 2001; Barbieri et al., 2010).”
BackgroundSTAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway
Pěnčík, J., Philippe, C., Schlederer, M., Atas, E., Pecoraro, M., Grund‐Gröschke, S., Li, W., Tracz, A., Heidegger, I. M., Lagger, S., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01825-8 · Cited by 52 · see citing works
“To generate constitutively activated Stat3, we took advantage of Stat3C/+ [32] and crossed them with PtenloxP/loxP mice.”
MethodSelf-citationLeehy, K. A., Truong, T. H., Mauro, L. J., & Lange, C. (2017) · Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2017.04.011 · Cited by 44 · see citing works
“genes that promote proliferation, survival, angiogenesis and stemness [80, 81].”
STAT3 Activities and Energy Metabolism: Dangerous Liaisons
Camporeale, A., Demaria, M., Monteleone, E., Giorgi, C., Wieckowski, M., Pinton, P., & Poli, V. (2014) · Cancers · doi:10.3390/cancers6031579 · Cited by 44 · see citing works
“Mice homozygous for the Stat3C k/in allele exhibited increased nuclear localization, prolonged Y-P and enhanced transcriptional activity in response to cytokine stimuli in several tissues as well as in mouse embryonic fibroblasts (MEFs) [40].”
Self-citationMolecular physiology of the tensin brotherhood of integrin adaptor proteins
Haynie, D. (2014) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.24560 · Cited by 43 · see citing works
Indirubin Derivative 6BIO Suppresses Metastasis
Braig, S., Kressirer, C. A., Liebl, J., Bischoff, F., Zahler, S., Meijer, L., & Vollmar, A. M. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4358 · Cited by 40 · see citing works
“© 2013 American Association for Cancercancerres.aacrjournals.org Downloaded from CTEN ti MMP2 A B CTEN ti MMP2 ac n 6BIO DMSO 3µM 10µM ac n siCtrl siJak1 Fig 4 Research. on August 18, 2017.”
BackgroundInfluentialC-Terminal Tensin-Like Gene Functions as an Oncogene and Promotes Cell Motility in Pancreatic Cancer
Al-ghamdi, S., Cachat, J., Albasri, A., Ahmed, M., Jackson, D., Zaitoun, A., Guppy, N., Otto, W., Alison, M., Kindle, K., et al. (2013) · Pancreas · doi:10.1097/mpa.0b013e3182557ceb · Cited by 40
“In addition, CTEN has been reported to be a target of Stat3 signaling, which, among other functions, stimulates cell motility.(11) Pancreatic cancer represents a disease with a dismal prognosis and an important burden on health care.”
BackgroundWang, M., Chen, G., Song, H., Hong, X., Yang, Z., & Sui, G. (2011) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2011.235 · Cited by 38 · see citing works
Challenging a Misnomer? The Role of Inflammatory Pathways in Inflammatory Breast Cancer
Morrow, R. J., Etemadi, N., Yeo, B., & Ernst, M. (2017) · Mediators of Inflammation · doi:10.1155/2017/4754827 · Cited by 38 · see citing works
“Constitutive activation of STAT3 has also shown to accelerate tumor progression and increase the metastatic potential in HER2-positive breast cancers [68].”
STAT3beta, a distinct isoform from STAT3
Zhang, H., Yang, P.-L., Li, E., & Xu, L. (2019) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2019.02.006 · Cited by 45 · see citing works
Caffarel, M., Zaragozá, R., Pensa, S., Li, J., Green, A., & Watson, C. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.122 · Cited by 37 · see citing works
“Stats 3 and 5 are activated in a high proportion of breast tumours,(8,9) and both have been shown to be mammary oncogenes.(10,11) In physiological conditions, JAK/Stat signalling is exquisitely controlled by a cohort of”
Self-citationSonnenblick, A., Uziely, B., Nechushtan, H., Kadouri, L., Galun, E., Axelrod, J., Katz, D., Daum, H., Hamburger, T., Maly, B., et al. (2013) · Breast Cancer Research and Treatment · doi:10.1007/s10549-013-2453-x · Cited by 36
Guyer, R. A., & Macara, I. G. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.621011 · Cited by 34 · see citing works
“STAT3 is a transcription factor that has been implicated in the initiation, progression, and metastasis of many cancers (19, 20).”
BackgroundMicroenvironment, Oncoantigens, and Antitumor Vaccination: Lessons Learned from BALB-neuT Mice
Conti, L., Ruiu, R., Barutello, G., Macagno, M., Bandini, S., Cavallo, F., & Lanzardo, S. (2014) · BioMed Research International · doi:10.1155/2014/534969 · Cited by 35 · see citing works
“Certainly, in BALB-neuTmice this network seems to be particularly interesting, as in a BALB-neuT mice knock-in for a constitutively active Stat3 allele, we observed an earlier and more invasive onset of mammary tumors [175].”
BackgroundSelf-citationLo, S.-H. (2014) · International Journal of Biochemistry and Cell Biology · doi:10.1016/j.biocel.2014.04.003 · Cited by 35
“…IGF-1 (insulin-like growth factor 1), IL-6 (interleukin 6) and IL-13 (interleukin 13) (Hung et al., 2013) mainly through the RAS-Raf-Mek, PI3K-Akt and Stat3 pathways activated by these cancer associated growth factors and cytokines (Hung et al., 2013, Barbieri et al., 2010, Al-Ghamdi et al., 2011).”
When Good Turns Bad: Regulation of Invasion and Metastasis by ErbB2 Receptor Tyrosine Kinase
Brix, D. M., Clemmensen, K. B., & Kallunki, T. (2014) · Cells · doi:10.3390/cells3010053 · Cited by 35 · see citing works
“Transgenic overexpression of mutated constitutively active Stat3 under the MMTV promoter together with MMTV-Neu induces Neu-mediated metastasis by upregulation of focal adhesion protein Cten [132] and genetic inactivation of a Stat3-responsive oncogene Bcl3 from MMTV-Neu mice dramatically reduces Neu-induced lung meta…”
BackgroundRegulation of pancreatic cancer aggressiveness by stromal stiffening
Rath, N., & Olson, M. (2016) · Nature Medicine · doi:10.1038/nm.4099 · Cited by 33 · see citing works
STAT3-induced WDR1 overexpression promotes breast cancer cell migration.
Lee, J. H., Kim, J. E., Kim, B., Han, H., Kang, S., & Cho, N. (2016) · Cellular Signalling · doi:10.1016/j.cellsig.2016.08.006 · Cited by 32
Zelenko, Z., & Gallagher, E. J. (2013) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.09.008 · Cited by 56 · see citing works
Up-Regulated Cten by FGF2 Contributes to FGF2-Mediated Cell Migration
Hung, S.-Y., Shih, Y.-P., Chen, M. J., & Lo, S.-H. (2013) · Molecular Carcinogenesis · doi:10.1002/mc.22034 · Cited by 32
“Cten expression promoted by IL-6 also echoes a recent report showing that IL-6 mediates cten up-regulation in a Jak-Stat3-dependent manner in MCF10A cells.[22] The positive effects on cten expression of FGF2, NGF, IL-13, PDGF, TGF-b, and IGF-1 have not been reported prior to current study.”
BackgroundThalappil, M. A., Butturini, E., de Prati, A. C., Bettin, I., Antonini, L., Sapienza, F., Garzoli, S., Ragno, R., & Mariotto, S. (2022) · Molecules · doi:10.3390/molecules27154834 · Cited by 31 · see citing works
Jin, J., Li, Y., Zhao, Q.-J., Chen, Y., Fu, S., & Wu, J.-B. (2021) · Cell communication and signaling : CCS · doi:10.1186/s12964-021-00705-2 · Cited by 31 · see citing works
“Moreover, the HA and A-FABPs induced STAT3 activation is directly associated with TAMs formation and enables the interaction between tumor cells and macrophages, such as promoting TGF-β1 and HIF-1α generation. c Node C: STAT3 cascade suppressed DCs differentiation and deprived the DCs ability to stimulate T cells.”
BackgroundInfluentialFicus carica Latex Prevents Invasion Through Induction of Let-7d Expression in GBM Cell Lines
Tezcan, G., Tunca, B., Bekar, A., Yalçın, M., Şahin, S., Budak, F., Cecener, G., Egeli, U., Demir, C., Guvenc, G., et al. (2015) · Cellular and molecular neurobiology · doi:10.1007/s10571-014-0109-y · Cited by 30
“Another well-known target of let-7d is Signal Transducer and Activator of Transcription 3 (STAT3) which is known to promote tumor cell proliferation, survival, and invasion (Ranger et al. 2009; Barbieri et al. 2010).”
BackgroundHesling, C., Lopez, J., Fattet, L., Gonzalo, P., Treilleux, I., Blanchard, D., Losson, R., Goffin, V., Pigat, N., Puisieux, A., et al. (2013) · Development · doi:10.1242/dev.085068 · Cited by 30
“Interestingly, it was recently demonstrated that STAT3 and STAT5 are activated in a high proportion of breast tumours (Diaz et al., 2006) and both have been shown to be mammary oncogenes in the mouse (Barbieri et al., 2010; Vafaizadeh et al., 2010).”
BackgroundAvalle, L., Incarnato, D., Savino, A., Gai, M., Marino, F., Pensa, S., Barbieri, I., Stadler, M. B., Provero, P., Oliviero, S., et al. (2017) · Cell Death and Differentiation · doi:10.1038/cdd.2017.103 · Cited by 28 · see citing works
“These tumors, which develop thanks to the ectopic expression of the rat Neu oncogene in the mammary epithelium, are more aggressive and invasive when mice also carry a constitutively active form of the transcription factor STAT3 (S3C).(28) Moreover, we show Figure 1 MiRs-143 and -145 modulate cell–cell contacts and mi…”
BackgroundMethodInfluentialSelf-citationThe Microrna-143/145 Cluster in Tumors: A Matter of Where and When
Poli, V., Seclì, L., & Avalle, L. (2020) · Cancers · doi:10.3390/cancers12030708 · Cited by 27
“We have recently demonstrated that miRs-143 and -145 are strongly overexpressed in the highly aggressive mouse mammary tumors that develop in mice expressing the NeuT oncogene together with constitutively active STAT3 [50,51].”
BackgroundSelf-citationMorrow, E., Pennel, K., Hatthakarnkul, P., Leslie, H., Mallon, E., Andersen, D., Jamieson, N., McMillan, D., Roseweir, A., & Edwards, J. (2023) · Cancer Medicine · doi:10.1002/cam4.6014 · Cited by 26
“11,12 There is limited evidence in the literature to date which explores IL6/JAK/ STAT3 as prognostic or predictive biomarkers in breast cancer.”
Genetic Interactions of STAT3 and Anticancer Drug Development
Fang, B. (2014) · Cancers · doi:10.3390/cancers6010494 · Cited by 24 · see citing works
“proliferation, survival, and invasion [1,2], mediate procarcinogenic inflammation while suppressing the host’s antitumor immunity [3], induce cancer stem cell renewal [4–6], enhance epithelial-mesenchymal transition [7,8] and angiogenesis [9,10], and generate positive autocrine and paracrine feedback loops”
BackgroundThe Molecular and Genetic Interactions between Obesity and Breast Cancer Risk
Ajabnoor, G. (2023) · Medicina · doi:10.3390/medicina59071338 · Cited by 22 · see citing works
“STAT3 is one downstream effector pathway for IL-6, and it is highly active in >50% of BCs, suggesting a cancer-promoting effect [106,107].”
BackgroundBennett, D. T., Reece, T., Foley, L. S., Sjoberg, A., Meng, X.-Z., Fullerton, D., & Weyant, M. (2014) · Journal of Thoracic and Cardiovascular Surgery · doi:10.1016/j.jtcvs.2014.08.087 · Cited by 24
“6 Elevated Cten expression recently has been shown to correlate with increased metastatic properties 7-10 in a number of in vitro and in vivo solid organ tumor models; however, the role of Cten in the invasive properties of lung cancer has not been evaluated.”
BackgroundIdentification of co-expression modules and pathways correlated with osteosarcoma and its metastasis
Wang, J.-S., Wang, Y.-G., Zhong, Y.-S., Li, X.-D., Du, S.-X., Xie, P., Zheng, G.-Z., & Han, J.-M. (2019) · World Journal of Surgical Oncology · doi:10.1186/s12957-019-1587-7 · Cited by 23
Qi, X.-M., Sun, L., Wan, J., Xu, R., He, S.-B., & Zhu, X.-G. (2020) · Pathology, Research and Practice · doi:10.1016/j.prp.2020.153001 · Cited by 22 · see citing works
The IL6-like Cytokine Family: Role and Biomarker Potential in Breast Cancer
Martínez-Pérez, C., Kay, C., Meehan, J., Gray, M., Dixon, J. M., & Turnbull, A. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11111073 · Cited by 27 · see citing works
“In BC, there is evidence of the expression and high signalling activity of STAT3 [89,287], which could be driven by aberrant JAK forms (reported in some clinical”
BackgroundOrecchia, V., Regis, G., Tassone, B., Valenti, C., Avalle, L., Saoncella, S., Calautti, E., & Poli, V. (2014) · Experimental Dermatology · doi:10.1111/exd.12585 · Cited by 22 · see citing works
Self-citationLu, X.-D., Gao, J., Zhang, Y., Zhao, T., Cai, H.-C., & Zhang, T.-R. (2018) · PLoS ONE · doi:10.1371/journal.pone.0198823 · Cited by 19
Multiple pathways regulate Cten in colorectal cancer without a Tensin switch
Thorpe, H., Akhlaq, M., Jackson, D., Ghamdi, S. A., Storr, S., Martin, S., & Ilyas, M. (2015) · International journal of experimental pathology (Print) · doi:10.1111/iep.12154 · Cited by 19
“There may be a difference in the effect in the cell lines used, but we have no explanation for the discrepancy between our results and those of Hung et al. (2013) and Barbieri et al. (2010).”
BackgroundResultInfluentialZhao, X.-Y., Mai, Z.-Z., Liu, L., Lu, Y., Cui, L., & Yu, J.-H. (2024) · International Journal on Biological Sciences · doi:10.7150/ijbs.86317 · Cited by 18
“In breast cancer, and specifically in highly aggressive and invasive inflammatory breast cancer, TNS4 overexpression was a notable feature [27].”
BackgroundOleuropein modulates glioblastoma miRNA pattern different from Olea europaea leaf extract
Tezcan, G., Aksoy, S., Tunca, B., Bekar, A., Mutlu, M., Cecener, G., Egeli, U., Kocaeli, H., Demirci, H., & Taskapilioglu, M. (2019) · Human and Experimental Toxicology · doi:10.1177/0960327119855123 · Cited by 17
Ablation of STAT3 in the B Cell Compartment Restricts Gammaherpesvirus Latency In Vivo
Reddy, S., Foreman, H., Sioux, T. O., Park, G. H., Poli, V., Reich, N., & Krug, L. (2016) · mBio · doi:10.1128/mbio.00723-16 · Cited by 17 · see citing works
Self-citationLoss of STAT3 in Lymphoma Relaxes NK Cell-Mediated Tumor Surveillance
Putz, E., Hoelzl, M., Baeck, J., Bagó-Horváth, Z., Schuster, C., Reichholf, B., Kern, D., Aberger, F., Sexl, V., & Hoelbl-Kovacic, A. (2014) · Cancers · doi:10.3390/cancers6010193 · Cited by 16
“Moreover, crossing of MMTV-neu transgenic mice to STAT3αC-knock-in animals resulted in an earlier onset of mammary tumor formation accompanied by increased invasiveness [13].”
Background
- Authors
- Barbieri, I., Pensa, S., Pannellini, T., Quaglino, E., Maritano, D., Demaria, M., Voster, A., Turkson, J., Cavallo, F., Watson, C. J., Provero, P., Musiani, P., & Poli, V.
- Affiliations
- University of Central Florida (US)
- ORCID
- Venue
- Cancer Research
- Published
- 2010-03-14
- Volume
- 70
- Issue
- 6
- Pages
- 2558-2567
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2004465485
- Cited by
- 148
- References
- 64
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 12 · 2022: 6 · 2021: 4 · 2020: 10 · 2019: 6 · 2018: 12 · 2017: 7 · 2016: 10 · 2015: 9 · 2014: 17 · 2013: 11 · 2012: 16
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Journal of International Crisis and Risk Communication Research (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- Fondazione CRT
- Ministero dell'Università e della Ricerca
- National Cancer Institute (R01CA128865)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- STAT3, CTEN, mammary tumors, breast cancer, tumor cell migration, tumor invasion, metastasis, neu oncogene, mouse mammary tumor virus, cell-cell contact, interleukin-6, inflammation and cancer, oncogenic signaling
- MeSH terms
- Tensins, Animals, Breast Neoplasms, Cell Movement, Cell Nucleus, Female, Humans, Lung Neoplasms, Male, Mammary Neoplasms, Experimental, Mice, Transgenic, Microfilament Proteins, Phosphorylation, Transcription, Genetic, Up-Regulation, Erb-b2 Receptor Tyrosine Kinases, Cell Line, Tumor, STAT3 Transcription Factor, Mice
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