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Panelo, L.C.; Machado, M.S.; Rubio, M.F.; Jaworski, F.; Alvarado, C.V.; Paz, L.A.; Urtreger, A.J.; Vazquez, E.; Costas, M.A. "High RAC3 expression levels are required for induction and maintaining of cancer cell stemness" (2018) Oncotarget. 9(5):5848-5860
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Abstract:

RAC3 is a transcription coactivator, usually overexpressed in several tumors and required to maintain the pluripotency in normal stem cells. In this work we studied the association between RAC3 overexpression on cancer cell stemness and the capacity of this protein to induce cancer stem properties in non tumoral cells. We performed in vitro and in vivo experiments using two strategies: by overexpressing RAC3 in the non tumoral cell line HEK293 and by silencing RAC3 in the human colorectal epithelial cell line HCT116 by transfection. Furthermore, we analysed public repository microarrays data from human colorectal tumors in different developmental stages. We found that RAC3 overexpression was mainly associated to CD133+ sidepopulation of colon cancer cells and also to early and advanced stages of colon cancer, involving increased expression of mesenchymal and stem markers. In turn, RAC3 silencing induced diminished tumoral properties and cancer stem cells as determined by Hoechst efflux, tumorspheres and clonogenic growth, which correlated with decreased Nanog and OCT4 expression. In non tumoral cells, RAC3 overexpression induced tumoral transformation; mesenchymal phenotype and stem markers expression. Moreover, these transformed cells generated tumors in vivo. Our results demonstrate that RAC3 is required for maintaining and induction of cancer cell stemness. © Panelo et al.

Registro:

Documento: Artículo
Título:High RAC3 expression levels are required for induction and maintaining of cancer cell stemness
Autor:Panelo, L.C.; Machado, M.S.; Rubio, M.F.; Jaworski, F.; Alvarado, C.V.; Paz, L.A.; Urtreger, A.J.; Vazquez, E.; Costas, M.A.
Filiación:Laboratorio de Biología Moleculary Apoptosis, Instituto de Investigaciones Médicas Alfredo Lanari, IDIM-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, C1427ARO, Argentina
Laboratorio de Anatomía Patológica, Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, C1427ARO, Argentina
Universidad de Buenos Aires, Instituto de Oncología 'Angel H Roffo', Area de Investigación, Buenos Aires, C1417DTB, Argentina
Laboratorio de Inflamación y Cancer, IQUIBICEN-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires, C1428EGA, Argentina
Argentine National Research Council (CONICET), Godoy Cruz (CABA)C1425FQB, Argentina
Palabras clave:Cancer stem cell; Mesenchymal cells; RAC3; Stem cells; Tumor; CD133 antigen; octamer transcription factor 4; protein RAC3; transcription factor; transcription factor NANOG; unclassified drug; advanced cancer; animal experiment; animal model; animal tissue; Article; cancer staging; cancer stem cell; clonogenesis; colorectal tumor; controlled study; embryo; epithelial mesenchymal transition; gene silencing; HCT 116 cell line; HEK293 cell line; human; human cell; in vitro study; in vivo study; male; malignant transformation; mesenchyme cell; microarray analysis; mouse; nonhuman; protein expression
Año:2018
Volumen:9
Número:5
Página de inicio:5848
Página de fin:5860
DOI: http://dx.doi.org/10.18632/oncotarget.23635
Título revista:Oncotarget
Título revista abreviado:Oncotarget
ISSN:19492553
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19492553_v9_n5_p5848_Panelo

Referencias:

  • Shackleton, M., Quintana, E., Fearon, E.R., Morrison, S.J., Heterogeneity in cancer: cancer stem cells versus clonal evolution (2009) Cell, 138, pp. 822-829. , https://doi.org/10.1016/j.cell.2009.08.017
  • Tysnes, B.B., Bjerkvig, R., Cancer initiation and progression: involvement of stem cells and the microenvironment (2007) Biochim Biophys Acta, 1775, pp. 283-297. , https://doi.org/10.1016/j.bbcan.2007.01.001
  • Soltysova, A., Altanerova, V., Altaner, C., Cancer stem cells (2005) Neoplasma, 52, pp. 435-440. , https://doi.org/://www.ncbi.nlm.nih.gov/pubmed/16284686
  • Liang, G., Zhang, Y., Genetic and epigenetic variations in iPSCs: potential causes and implications for application (2013) Cell Stem Cell, 13, pp. 149-159. , https://doi.org/10.1016/j.stem.2013.07.001
  • Li, Z., CD133: a stem cell biomarker and beyond (2013) Exp Hematol Oncol, 2, p. 17. , https://doi.org/10.1186/2162-3619-2-17
  • Tang, D.G., Understanding cancer stem cell heterogeneity and plasticity (2012) Cell Res, 22, pp. 457-472. , https://doi.org/10.1038/cr.2012.13
  • Li, H., Gomes, P.J., Chen, J.D., RAC3, a steroid/nuclear receptor-associated coactivator that is related to SRC-1 and TIF2 (1997) Proc Natl Acad Sci USA, 94, pp. 8479-8484. , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC22964/
  • Yan, J., Tsai, S.Y., Tsai, M.J., SRC-3/AIB1: transcriptional coactivator in oncogenesis (2006) Acta Pharmacol Sin, 27, pp. 387-394. , https://doi.org/10.1111/j.1745-7254.2006.00315.x
  • Ma, G., Ren, Y., Wang, K., He, J., SRC-3 has a role in cancer other than as a nuclear receptor coactivator (2011) Int J Biol Sci, 7, pp. 664-672. , http://www.ncbi.nlm.nih.gov/pubmed/21647249
  • Torres-Arzayus, M.I., Font Mora, J., Yuan, J., Vazquez, F., Bronson, R., Rue, M., Sellers, W.R., Brown, M., High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene (2004) Cancer Cell, 6, pp. 263-274. , https://doi.org/10.1016/j.ccr.2004.06.027
  • Anzick, S.L., Kononen, J., Walker, R.L., Azorsa, D.O., Tanner, M.M., Guan, X.Y., Sauter, G., Meltzer, P.S., AIB1, a steroid receptor coactivator amplified in breast and ovarian cancer (1997) Science, 277, pp. 965-968. , https://doi.org/10.1126/science.277.5328.965
  • Werbajh, S., Nojek, I., Lanz, R., Costas, M.A., RAC-3 is a NF-kB coactivator (2000) FEBS Lett, 485, pp. 195-199. , https://doi.org/10.1016/S0014-5793(00)02223-7
  • Henke, R.T., Haddad, B.R., Kim, S.E., Rone, J.D., Mani, A., Jessup, J.M., Wellstein, A., Riegel, A.T., Overexpression of the nuclear receptor coactivator AIB1 (SRC-3) during progression of pancreatic adenocarcinoma (2004) Clin Cancer Res, 10, pp. 6134-6142. , https://doi.org/10.1158/1078-0432.CCR-04-0561
  • Sakakura, C., Hagiwara, A., Yasuoka, R., Fujita, Y., Nakanishi, M., Masuda, K., Kimura, A., Yamagishi, H., Amplification and over-expression of the AIB1 nuclear receptor co-activator gene in primary gastric cancers (2000) Int J Cancer, 89, pp. 217-223
  • Zhou, H.J., Yan, J., Luo, W., Ayala, G., Lin, S.H., Erdem, H., Ittmann, M., Tsai, M.J., SRC-3 is required for prostate cancer cell proliferation and survival (2005) Cancer Res, 65, pp. 7976-7983. , https://doi.org/10.1158/0008-5472.CAN-04-4076
  • Colo, G.P., Rubio, M.F., Nojek, I.M., Werbajh, S.E., Echeverria, P.C., Alvarado, C.V., Nahmod, V.E., Costas, M.A., The p160 nuclear receptor co-activator RAC3 exerts an antiapoptotic role through a cytoplasmatic action (2008) Oncogene, 27, pp. 2430-2444. , https://doi.org/10.1038/sj.onc.1210900
  • Wang, M., Zhao, F., Li, S., Chang, A.K., Jia, Z., Chen, Y., Xu, F., Wu, H., AIB1 cooperates with ERalpha to promote epithelial mesenchymal transition in breast cancer through SNAI1 activation (2013) PLoS One, 8. , https://doi.org/10.1371/journal.pone.0065556
  • Colo, G.P., Rosato, R.R., Grant, S., Costas, M.A., RAC3 downregulation sensitizes human chronic myeloid leukemia cells to TRAIL-induced apoptosis (2007) FEBS Lett, 581, pp. 5075-5081. , https://doi.org/10.1016/j.febslet.2007.09.052
  • Fernandez Larrosa, P.N., Alvarado, C.V., Rubio, M.F., Ruiz Grecco, M., Micenmacher, S., Martinez-Noel, G.A., Panelo, L., Costas, M.A., Nuclear receptor coactivator RAC3 inhibits autophagy (2012) Cancer Sci, 103, pp. 2064-2071. , https://doi.org/10.1111/cas.12019
  • Fernández Larrosa, P.N., Ruíz Grecco, M., Mengual Gómez, D., Alvarado, C.V., Panelo, L.C., Rubio, M.F., Alonso, D.F., Costas, M.A., RAC3 more than a nuclear receptor coactivator: a key inhibitor of senescence that is downregulated in aging (2015) Cell Death Dis, 6
  • Qin, L., Liao, L., Redmond, A., Young, L., Yuan, Y., Chen, H., O'Malley, B.W., Xu, J., The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expression (2008) Mol Cell Biol, 28, pp. 5937-5950. , https://doi.org/10.1128/MCB.00579-08
  • Tomar, A., Schlaepfer, D.D., A PAK-activated linker for EGFR and FAK (2010) Dev Cell, 18, pp. 170-172. , https://doi.org/10.1016/j.devcel.2010.01.013
  • Long, W., Yi, P., Amazit, L., LaMarca, H.L., Ashcroft, F., Kumar, R., Mancini, M.A., O'Malley, B.W., SRC-3Delta4 mediates the interaction of EGFR with FAK to promote cell migration (2010) Mol Cell, 37, pp. 321-332. , https://doi.org/10.1016/j.molcel.2010.01.004
  • Rubio, M.F., Fernandez, P.N., Alvarado, C.V., Panelo, L.C., Grecco, M.R., Colo, G.P., Martinez-Noel, G.A., Costas, M.A., Cyclin D1 is a NF-kappaB corepressor (2012) Biochim Biophys Acta, 1823, pp. 1119-1131. , https://doi.org/10.1016/j.bbamcr.2012.01.009
  • Wu, Z., Yang, M., Liu, H., Guo, H., Wang, Y., Cheng, H., Chen, L., Role of nuclear receptor coactivator 3 (Ncoa3) in pluripotency maintenance (2012) J Biol Chem, 287, pp. 38295-38304. , https://doi.org/10.1074/jbc.M112.373092
  • Percharde, M., Azuara, V., Essential roles for the nuclear receptor coactivator Ncoa3 in pluripotency (2013) Cell Cycle, 12, pp. 195-196. , https://doi.org/10.4161/cc.23377
  • Percharde, M., Lavial, F., Ng, J.H., Kumar, V., Tomaz, R.A., Martin, N., Yeo, J.C., Azuara, V., Ncoa3 functions as an essential Esrrb coactivator to sustain embryonic stem cell self-renewal and reprogramming (2012) Genes Dev, 26, pp. 2286-2298. , https://doi.org/10.1101/gad.195545.112
  • Chitilian, J.M., Thillainadesan, G., Manias, J.L., Chang, W.Y., Walker, E., Isovic, M., Stanford, W.L., Torchia, J., Critical components of the pluripotency network are targets for the p300/CBP interacting protein (p/CIP) in embryonic stem cells (2014) Stem Cells, 32, pp. 204-215. , https://doi.org/10.1002/stem.1564
  • Alvarado, C.V., Rubio, M.F., Fernández Larrosa, P.N., Panelo, L.C., Azurmendi, P.J., Ruiz Grecco, M., Martínez-Nöel, G.A., Costas, M.A., The levels of RAC3 expression are up regulated by TNF in the inflammatory response (2014) FEBS Open Bio, 4, pp. 450-457. , https://doi.org/10.1016/j.fob.2014.04.009
  • Marcucci, F., Ghezzi, P., Rumio, C., The role of autophagy in the cross-talk between epithelial-mesenchymal transitioned tumor cells and cancer stem-like cells (2017) Mol Cancer, 16, p. 3. , https://doi.org/10.1186/s12943-016-0573-8
  • Gonzalez, D.M., Medici, D., Signaling mechanisms of the epithelial-mesenchymal transition (2014) Sci Signal, 7. , https://doi.org/10.1126/scisignal.2005189
  • Seigel, G.M., Campbell, L.M., High-throughput microtiter assay for Hoechst 33342 dye uptake (2004) Cytotechnology, 45, pp. 155-160. , https://doi.org/10.1007/s10616-004-7256-9
  • Okita, K., Ichisaka, T., Yamanaka, S., Generation of germlinecompetent induced pluripotent stem cells (2007) Nature, 448, pp. 313-317. , https://doi.org/10.1038/nature05934
  • Williams, K., Motiani, K., Giridhar, P.V., Kasper, S., CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches (2013) Exp Biol Med (Maywood), 238, pp. 324-338. , https://doi.org/10.1177/1535370213480714
  • Weissman, I.L., Stem cells are units of natural selection for tissue formation, for germline development, and in cancer development (2015) Proc Natl Acad Sci USA, 112, pp. 8922-8928. , https://doi.org/10.1073/pnas.1505464112
  • Clarke, M.F., Dick, J.E., Dirks, P.B., Eaves, C.J., Jamieson, C.H., Jones, D.L., Visvader, J., Wahl, G.M., Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells (2006) Cancer Res, 66, pp. 9339-9344. , https://doi.org/10.1158/0008-5472.CAN-06-3126
  • Beachy, P.A., Karhadkar, S.S., Berman, D.M., Tissue repair and stem cell renewal in carcinogenesis (2004) Nature, 432, pp. 324-331. , https://doi.org/10.1038/nature03100
  • Pardal, R., Clarke, M.F., Morrison, S.J., Applying the principles of stem-cell biology to cancer (2003) Nat Rev Cancer, 3, pp. 895-902. , https://doi.org/10.1038/nrc1232
  • Zhang, S.N., Huang, F.T., Huang, Y.J., Zhong, W., Yu, Z., Characterization of a cancer stem cell-like side population derived from human pancreatic adenocarcinoma cells (2010) Tumori, 96, pp. 985-992. , http://www.ncbi.nlm.nih.gov/pubmed/21388063
  • Zhang, Y., Toy, K.A., Kleer, C.G., Metaplastic breast carcinomas are enriched in markers of tumor-initiating cells and epithelial to mesenchymal transition (2012) Mod Pathol, 25, pp. 178-184. , https://doi.org/10.1038/modpathol.2011.167
  • Balkwill, F., Mantovani, A., Inflammation and cancer: back to Virchow? (2001) Lancet, 357, pp. 539-545. , https://doi.org/10.1016/S0140-6736(00)04046-0
  • Karin, M., Greten, F.R., NF-kappaB: linking inflammation and immunity to cancer development and progression (2005) Nat Rev Immunol, 5, pp. 749-759. , https://doi.org/10.1038/nri1703
  • Urtreger, A.J., Grossoni, V.C., Falbo, K.B., Kazanietz, M.G., Bal Kier Joffe, E.D., Atypical protein kinase C-zeta modulates clonogenicity, motility, and secretion of proteolytic enzymes in murine mammary cells (2005) Mol Carcinog, 42, pp. 29-39. , https://doi.org/10.1002/mc.20066
  • Berardi, D.E., Flumian, C., Rodriguez, C.E., Bessone, M.I., Cirigliano, S.M., Joffe, E.D., Fiszman, G.L., Todaro, L.B., PKCdelta Inhibition Impairs Mammary Cancer Proliferative Capacity But Selects Cancer Stem Cells, Involving Autophagy (2016) J Cell Biochem, 117, pp. 730-740. , https://doi.org/10.1002/jcb.25358
  • Berardi, D.E., Flumian, C., Campodónico, P.B., Urtreger, A.J., Diaz Bessone, M.I., Motter, A.N., Bal Kier Joffé, E.D., Todaro, L.B., Myoepithelial and luminal breast cancer cells exhibit different responses to all-trans retinoic acid (2015) Cell Oncol (Dordr), 38, pp. 289-305
  • Gueron, G., Giudice, J., Valacco, P., Paez, A., Elguero, B., Toscani, M., Jaworski, F., Vazquez, E., Heme-oxygenase-1 implications in cell morphology and the adhesive behavior of prostate cancer cells (2014) Oncotarget, 5, pp. 4087-4102. , https://doi.org/10.18632/oncotarget.1826

Citas:

---------- APA ----------
Panelo, L.C., Machado, M.S., Rubio, M.F., Jaworski, F., Alvarado, C.V., Paz, L.A., Urtreger, A.J.,..., Costas, M.A. (2018) . High RAC3 expression levels are required for induction and maintaining of cancer cell stemness. Oncotarget, 9(5), 5848-5860.
http://dx.doi.org/10.18632/oncotarget.23635
---------- CHICAGO ----------
Panelo, L.C., Machado, M.S., Rubio, M.F., Jaworski, F., Alvarado, C.V., Paz, L.A., et al. "High RAC3 expression levels are required for induction and maintaining of cancer cell stemness" . Oncotarget 9, no. 5 (2018) : 5848-5860.
http://dx.doi.org/10.18632/oncotarget.23635
---------- MLA ----------
Panelo, L.C., Machado, M.S., Rubio, M.F., Jaworski, F., Alvarado, C.V., Paz, L.A., et al. "High RAC3 expression levels are required for induction and maintaining of cancer cell stemness" . Oncotarget, vol. 9, no. 5, 2018, pp. 5848-5860.
http://dx.doi.org/10.18632/oncotarget.23635
---------- VANCOUVER ----------
Panelo, L.C., Machado, M.S., Rubio, M.F., Jaworski, F., Alvarado, C.V., Paz, L.A., et al. High RAC3 expression levels are required for induction and maintaining of cancer cell stemness. Oncotarget. 2018;9(5):5848-5860.
http://dx.doi.org/10.18632/oncotarget.23635