Artículo

Tocci, J.M.; Felcher, C.M.; García Sola, M.E.; Goddio, M.V.; Zimberlin, M.N.; Rubinstein, N.; Srebrow, A.; Coso, O.A.; Abba, M.C.; Meiss, R.P.; Kordon, E.C. "R-Spondin3 is associated with basal-progenitor behavior in normal and tumor mammary cells" (2018) Cancer Research. 78(16):4497-4511
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Abstract:

R-spondin3 (RSPO3) is a member of a family of secreted proteins that enhance Wnt signaling pathways in diverse processes, including cancer. However, the role of RSPO3 in mammary gland and breast cancer development remains unclear. In this study, we show that RSPO3 is expressed in the basal stem cell–enriched compartment of normal mouse mammary glands but is absent from committed mature luminal cells in which exogenous RSPO3 impairs lactogenic differentiation. RSPO3 knockdown in basal-like mouse mammary tumor cells reduced canonical Wnt signaling, epithelial-to-mesenchymal transition-like features, migration capacity, and tumor formation in vivo. Conversely, RSPO3 overexpression, which was associated with some LGR and RUNX factors, highly correlated with the basal-like subtype among patients with breast cancer. Thus, we identified RSPO3 as a novel key modulator of breast cancer development and a potential target for treatment of basal-like breast cancers. Significance: These findings identify RSPO3 as a potential therapetuic target in basal-like breast cancers. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4497/F1.large.jpg. 2018 American Association for Cancer Research.

Registro:

Documento: Artículo
Título:R-Spondin3 is associated with basal-progenitor behavior in normal and tumor mammary cells
Autor:Tocci, J.M.; Felcher, C.M.; García Sola, M.E.; Goddio, M.V.; Zimberlin, M.N.; Rubinstein, N.; Srebrow, A.; Coso, O.A.; Abba, M.C.; Meiss, R.P.; Kordon, E.C.
Filiación:CONICET-Universidad de Buenos Aires, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Buenos Aires, Argentina
Departamento de Fisiología, Biología Molecular y Celular, Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina
Basic and Applied Immunological Research Center, School of Medicine, National University of La Plata, La Plata, Argentina
Department of Pathology, Institute of Oncology Studies, National Academy of Medicine, Buenos Aires, Argentina
Facultad de Ciencias Exactas y Naturales, Departamento de Química Biologica, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:G protein coupled receptor; leucine rich repeat containing G protein coupled receptor; protein; R spondin3; transcription factor RUNX; unclassified drug; adult; animal cell; animal experiment; animal model; animal tissue; Article; basal like breast cancer; breast carcinogenesis; breast cell; cancer cell; cancer growth; cell differentiation; cell migration; controlled study; epithelial mesenchymal transition; female; gene; gene knockdown; gene overexpression; gene targeting; human; human cell; human tissue; in vivo study; mouse; nonhuman; priority journal; protein expression; RSPO3 gene; stem cell; Wnt signaling
Año:2018
Volumen:78
Número:16
Página de inicio:4497
Página de fin:4511
DOI: http://dx.doi.org/10.1158/0008-5472.CAN-17-2676
Título revista:Cancer Research
Título revista abreviado:Cancer Res.
ISSN:00085472
CODEN:CNREA
CAS:protein, 67254-75-5
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00085472_v78_n16_p4497_Tocci

Referencias:

  • de Lau, W.B., Snel, B., Clevers, H.C., The R-spondin protein family (2012) Genome Biol, 13, p. 242
  • Kamata, T., Katsube, K.-I., Michikawa, M., Yamada, M., Takada, S., Mizusawa, H., R-spondin, a novel gene with thrombospondin type 1 domain, was expressed in the dorsal neural tube and affected in Wnts mutants (2004) Biochim Biophys Acta, 1676, pp. 51-62
  • Kazanskaya, O., Glinka, A., Del Barco Barrantes, I., Stannek, P., Niehrs, C., Wu, W., R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis (2004) Dev Cell, 7, pp. 525-534
  • Ohkawara, B., Glinka, A., Niehrs, C., Rspo3 binds syndecan 4 and induces Wnt/PCP signaling via clathrin-mediated endocytosis to promote morphogenesis (2011) Dev Cell, 20, pp. 303-314
  • Carmon, K.S., Gong, X., Lin, Q., Thomas, A., Liu, Q., R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to regulate Wnt/b-catenin signaling (2011) Proc Natl Acad Sci U S A, 108, pp. 11452-11457
  • Glinka, A., Dolde, C., Kirsch, N., Huang, Y.L., Kazanskaya, O., Ingelfinger, D., LGR4 and LGR5 are R-spondin receptors mediating Wnt/beta-catenin and Wnt/PCP signalling (2011) EMBO Rep, 12, pp. 1055-1061
  • de Lau, W., Peng, W.C., Gros, P., Clevers, H., The R-spondin/Lgr5/Rnf43 module: Regulator of Wnt signal strength (2014) Genes Dev, 28, pp. 305-316
  • Clevers, H., Nusse, R., Wnt/beta-catenin signaling and disease (2012) Cell, 149, pp. 1192-1205
  • Sternlicht, M.D., Key stages in mammary gland development: The cues that regulate ductal branching morphogenesis (2006) Breast Cancer Res, 8, p. 201
  • Macias, H., Hinck, L., Mammary gland development (2012) Wiley Interdiscip Rev Dev Biol, 1, pp. 533-557
  • Zeng, Y.A., Nusse, R., Wnt proteins are self-renewing factors for mammary stem cells and promote their long-term expansion in vivo (2010) Cell Stem Cell, 6, pp. 568-577
  • Kordon, E.C., Smith, G.H., Anentirefunctionalmammaryglandmaycomprise the progeny from a single cell (1998) Development, 125, pp. 1921-1930
  • Plaks, V., Brenot, A., Lawson, D.A., Linnemann, J.R., Van Kappel, E.C., Wong, K.C., Lgr5-expressing cells are sufficient and necessary for postnatal mammary gland organogenesis (2013) Cell Rep, 3, pp. 70-78
  • Wang, Y., Dong, J., Li, D., Lai, L., Siwko, S., Li, Y., Lgr4 regulates mammary gland development and stem cell activity through the pluripotency transcription factor Sox2 (2013) Stem Cells, 31, pp. 1921-1931
  • Chu, E.Y., Hens, J., Andl, T., Kairo, A., Yamaguchi, T.P., Brisken, C., Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis (2004) Development, 131, pp. 4819-4829
  • Van Amerongen, R., Bowman, A.N., Nusse, R., Developmental stage and time dictate the fate of Wnt/beta-catenin-responsive stem cells in the mammary gland (2012) Cell Stem Cell, 11, pp. 387-400
  • Yu, Q.C., Verheyen, E.M., Zeng, Y.A., Mammary Development and Breast Cancer: A Wnt Perspective (2016) Cancers, 8, p. 65. , Basel
  • Klauzinska, M., Baljinnyam, B., Raafat, A., Rodriguez-Canales, J., Strizzi, L., Endo Greer, Y., Rspo2/Int7 regulates invasiveness and tumorigenic properties of mammary epithelial cells (2012) J Cell Physiol, 227, pp. 1960-1971
  • Seshagiri, S., Stawiski, E.W., Durinck, S., Modrusan, Z., Storm, E.E., Conboy, C.B., Recurrent R-spondin fusions in colon cancer (2012) Nature, 488, pp. 660-664
  • Hao, H.X., Jiang, X., Cong, F., Control of Wnt receptor turnover by R-spondin-ZNRF3/RNF43 signaling module and its dysregulation in cancer (2016) Cancers, 8, p. 54. , Basel
  • Kazanskaya, O., Ohkawara, B., Heroult, M., Wu, W., Maltry, N., Augustin, H.G., The Wnt signaling regulator R-spondin 3 promotes angioblast and vascular development (2008) Development, 135, pp. 3655-3664
  • Scholz, B., Korn, C., Wojtarowicz, J., Mogler, C., Augustin, I., Boutros, M., Endothelial RSPO3 controls vascular stability and pruning through non-canonical WNT/Ca2þ/NFAT signaling (2016) Dev Cell, 36, pp. 79-93
  • Kabiri, Z., Greicius, G., Madan, B., Biechele, S., Zhong, Z., Zaribafzadeh, H., Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts (2014) Development, 141, pp. 2206-2215
  • Gong, X., Yi, J., Carmon, K.S., Crumbley, C.A., Xiong, W., Thomas, A., Aberrant RSPO3-LGR4 signaling in Keap1-deficient lung adenocarcinomas promotes tumor aggressiveness (2015) Oncogene, 34, pp. 4692-4701
  • Chartier, C., Raval, J., Axelrod, F., Bond, C., Cain, J., Dee-Hoskins, C., Therapeutic targeting of tumor-derived R-spondin attenuates beta-catenin signaling and tumorigenesis in multiple cancer types (2016) Cancer Res, 76, pp. 713-723
  • Gattelli, A., Zimberlin, M.N., Meiss, R.P., Castilla, L.H., Kordon, E.C., Selection of early-occurring mutations dictates hormone-independent progression in mouse mammary tumor lines (2006) J Virol, 80, pp. 11409-11415
  • Theodorou, V., Kimm, M.A., Boer, M., Wessels, L., Theelen, W., Jonkers, J., MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer (2007) Nat Genet, 39, pp. 759-769
  • Berardi, D.E., Flumian, C., Campodonico, P.B., Urtreger, A.J., Diaz Bessone, M.I., Motter, A.N., Myoepithelial and luminal breast cancer cells exhibit different responses to all-trans retinoic acid (2015) Cell Oncol (Dordr), 38, pp. 289-305
  • Prat, A., Parker, J.S., Karginova, O., Fan, C., Livasy, C., Herschkowitz, J.I., Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer (2010) Breast Cancer Res, 12, p. R68
  • Williams, C., Helguero, L., Edvardsson, K., Haldosen, L.A., Gustafsson, J.A., Gene expression in murine mammary epithelial stem cell-like cells shows similarities to human breast cancer gene expression (2009) Breast Cancer Res, 11, p. R26
  • Korkaya, H., Paulson, A., Charafe-Jauffret, E., Ginestier, C., Brown, M., Dutcher, J., Regulation of mammary stem/progenitor cells by PTEN/Akt/b-catenin signaling (2009) PLoS Biol, 7
  • Livasy, C.A., Karaca, G., Nanda, R., Tretiakova, M.S., Olopade, O.I., Moore, D.T., Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma (2006) Mod Pathol, 19, pp. 264-271
  • Recouvreux, M.S., Grasso, E.N., Echeverria, P.C., Rocha-Viegas, L., Castilla, L.H., Schere-Levy, C., RUNX1 and FOXP3 interplay regulates expression of breast cancer related genes (2016) Oncotarget, 7, pp. 6552-6565
  • Blick, T., Hugo, H., Widodo, E., Waltham, M., Pinto, C., Mani, S.A., Epithelial mesenchymal transition traits in human breast cancer cell lines parallel the CD44hi/CD24lo/- Stem cell phenotype in human breast cancer (2010) J Mammary Gland Biol Neoplasia, 15, pp. 235-252
  • Gilles, C., Polette, M., Mestdagt, M., Nawrocki-Raby, B., Ruggeri, P., Birembaut, P., Transactivation of vimentin by b-catenin in human breast cancer cells (2003) Cancer Res, 63, pp. 2658-2664
  • Cai, C., Yu, Q.C., Jiang, W., Liu, W., Song, W., Yu, H., R-spondin1 is a novel hormone mediator for mammary stem cell self-renewal (2014) Genes Dev, 28, pp. 2205-2218
  • DiMeo, T.A., Anderson, K., Phadke, P., Feng, C., Perou, C.M., Naber, S., A novel lung metastasis signature links Wnt signaling with cancer cell self-renewal and epithelial-mesenchymal transition in basal-like breast cancer (2009) Cancer Res, 69, pp. 5364-5373
  • Micalizzi, D.S., Farabaugh, S.M., Ford, H.L., Epithelial-mesenchymal transition in cancer: Parallels between normal development and tumor progression (2010) J Mammary Gland Biol Neoplasia, 15, pp. 117-134
  • Cichon, M.A., Nelson, C.M., Radisky, D.C., Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion (2015) Cancer Informatics, 14, pp. 1-13
  • Nelson, C.M., VanDuijn, M.M., Inman, J.L., Fletcher, D.A., Bissell, M.J., Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures (2006) Science, 314, p. 298
  • Kouros-Mehr, H., Werb, Z., Candidate regulators of mammary branching morphogenesis identified by genome-wide transcript analysis (2006) Dev Dyn, 235, pp. 3404-3412
  • Matsuda, Y., Schlange, T., Oakeley, E.J., Boulay, A., Hynes, N.E., WNT signaling enhances breast cancer cell motility and blockade of the WNT pathway by sFRP1 suppresses MDA-MB-231 xenograft growth (2009) Breast Cancer Res, 11, p. R32
  • Xu, J., Prosperi, J.R., Choudhury, N., Olopade, O.I., Goss, K.H., Beta-Catenin is required for the tumorigenic behavior of triple-negative breast cancer cells (2015) PLoS One, 10
  • Constantinou, T., Baumann, F., Lacher, M.D., Saurer, S., Friis, R., Dharmarajan, A., SFRP-4 abrogates Wnt-3a-induced b-catenin and Akt/PKB signalling and reverses a Wnt-3a-imposed inhibition of in vitro mammary differentiation (2008) J Mol Signal, 3, p. 10
  • Zhang, M., Atkinson, R.L., Rosen, J.M., Selective targeting of radiation-resistant tumor-initiating cells (2010) Proc Natl Acad Sci U S A, 107, pp. 3522-3527
  • Creighton, C.J., Li, X., Landis, M., Dixon, J.M., Neumeister, V.M., Sjolund, A., Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features (2009) Proc Natl Acad Sci U S A, 106, pp. 13820-13825
  • Vadnais, C., Shooshtarizadeh, P., Rajadurai, C.V., Lesurf, R., Hulea, L., Davoudi, S., Autocrine activation of the Wnt/beta-catenin pathway by CUX1 and GLIS1 in breast cancers (2014) Biol Open, 3, pp. 937-946
  • Khramtsov, A.I., Khramtsova, G.F., Tretiakova, M., Huo, D., Olopade, O.I., Goss, K.H., Wnt/b-catenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome (2010) Am J Pathol, 176, pp. 2911-2920
  • Lopez-Knowles, E., Zardawi, S.J., McNeil, C.M., Millar, E.K.A., Crea, P., Musgrove, E.A., Cytoplasmic localization of b-catenin is a marker of poor outcome in breast cancer patients (2010) Cancer Epidemiol Biomarkers Prev, 19, pp. 301-309
  • Geyer, F.C., Lacroix-Triki, M., Savage, K., Arnedos, M., Lambros, M.B., MacKay, A., Beta-Catenin pathway activation in breast cancer is associated with triple-negative phenotype but not with CTNNB1 mutation (2011) Mod Pathol, 24, pp. 209-231
  • Rooney, N., Riggio, A.I., Mendoza-Villanueva, D., Shore, P., Cameron, E.R., Blyth, K., Runx genes in breast cancer and the mammary lineage (2017) RUNX Proteins in Development and Cancer, pp. 353-368. , Groner Y, Ito Y, Liu Neil JC, Speck NA, van Wijnen A, editors. Singapore: Springer
  • Pfefferle, A.D., Spike, B.T., Wahl, G.M., Perou, C.M., Luminal progenitor and fetal mammary stem cell expression features predict breast tumor response to neoadjuvant chemotherapy (2015) Breast Cancer Res Treat, 149, pp. 425-437

Citas:

---------- APA ----------
Tocci, J.M., Felcher, C.M., García Sola, M.E., Goddio, M.V., Zimberlin, M.N., Rubinstein, N., Srebrow, A.,..., Kordon, E.C. (2018) . R-Spondin3 is associated with basal-progenitor behavior in normal and tumor mammary cells. Cancer Research, 78(16), 4497-4511.
http://dx.doi.org/10.1158/0008-5472.CAN-17-2676
---------- CHICAGO ----------
Tocci, J.M., Felcher, C.M., García Sola, M.E., Goddio, M.V., Zimberlin, M.N., Rubinstein, N., et al. "R-Spondin3 is associated with basal-progenitor behavior in normal and tumor mammary cells" . Cancer Research 78, no. 16 (2018) : 4497-4511.
http://dx.doi.org/10.1158/0008-5472.CAN-17-2676
---------- MLA ----------
Tocci, J.M., Felcher, C.M., García Sola, M.E., Goddio, M.V., Zimberlin, M.N., Rubinstein, N., et al. "R-Spondin3 is associated with basal-progenitor behavior in normal and tumor mammary cells" . Cancer Research, vol. 78, no. 16, 2018, pp. 4497-4511.
http://dx.doi.org/10.1158/0008-5472.CAN-17-2676
---------- VANCOUVER ----------
Tocci, J.M., Felcher, C.M., García Sola, M.E., Goddio, M.V., Zimberlin, M.N., Rubinstein, N., et al. R-Spondin3 is associated with basal-progenitor behavior in normal and tumor mammary cells. Cancer Res. 2018;78(16):4497-4511.
http://dx.doi.org/10.1158/0008-5472.CAN-17-2676