High RAC3 expression levels are required for induction and maintaining of cancer cell stemness

Oncotarget
L C PaneloMónica A Costas

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 performedin vitroandin vivoexperiments 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+ side-population 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 ...Continue Reading

References

Aug 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·H LiJ D Chen
Nov 30, 2000·FEBS Letters·S WerbajhM A Costas
Mar 7, 2001·Lancet·F Balkwill, A Mantovani
Jan 23, 2004·Nature Reviews. Cancer·Ricardo PardalSean J Morrison
Sep 28, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ralf Thorsten HenkeAnna Tate Riegel
Nov 17, 2004·Molecular Carcinogenesis·Alejandro J UrtregerElisa D Bal de Kier Joffé
Nov 19, 2004·Nature·Philip A BeachyDavid M Berman
Sep 6, 2005·Cancer Research·Hai-Jun ZhouMing-Jer Tsai
Sep 22, 2005·Nature Reviews. Immunology·Michael Karin, Florian R Greten
Mar 17, 2006·Acta Pharmacologica Sinica·Jun YanMing-Jer Tsai
Mar 22, 2007·Biochimica Et Biophysica Acta·Berit B Tysnes, Rolf Bjerkvig
Jun 8, 2007·Nature·Keisuke OkitaShinya Yamanaka
Nov 13, 2008·Cytotechnology·Gail M Seigel, Lorrie M Campbell
Sep 10, 2009·Cell·Mark ShackletonSean J Morrison
Feb 18, 2010·Molecular Cell·Weiwen LongBert W O'Malley
Feb 18, 2010·Developmental Cell·Alok Tomar, David D Schlaepfer
Jun 8, 2011·International Journal of Biological Sciences·Gang MaJianjun He
Nov 15, 2011·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Yanhong ZhangCelina G Kleer
Feb 7, 2012·Biochimica Et Biophysica Acta·María F RubioMónica A Costas
Feb 24, 2012·Cell Research·Dean G Tang
Sep 11, 2012·Cancer Science·Pablo Nicolas Fernandez LarrosaMonica Alejandra Costas
Sep 15, 2012·The Journal of Biological Chemistry·Zhaoting WuLingyi Chen
Jan 5, 2013·Cell Cycle·Michelle Percharde, Véronique Azuara
Apr 20, 2013·Experimental Biology and Medicine·Karin WilliamsSusan Kasper
Jul 3, 2013·Experimental Hematology & Oncology·Zhong Li
Jun 12, 2014·FEBS Open Bio·Cecilia Viviana AlvaradoMónica Alejandra Costas
Sep 25, 2014·Science Signaling·David M Gonzalez, Damian Medici
Jul 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Irving L Weissman
Sep 4, 2015·Journal of Cellular Biochemistry·Damián E BerardiLaura B Todaro

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Citations

Oct 2, 2019·Nutrition and Cancer·Mileni Soares MachadoMónica A Costas
Aug 5, 2020·Biomarkers in Medicine·Jing QuanQi Zhang
Feb 23, 2021·Cellular Oncology (Dordrecht)·Alejandra Graciela PalmaMónica Alejandra Costas

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Datasets Mentioned

BETA
GDS4718
GSM932995
GSE24747
GPL570
GPL6244

Methods Mentioned

BETA
transgenic
FACS
flow cytometry
genetic modification
FCS
fluorescence microscopy
Protein Assay

Software Mentioned

Image J

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