LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer

Oncotarget
Masami NozakiHiroshi Nojima

Abstract

Cancer stem cells (CSCs), which play important roles in tumor initiation and progression, are resistant to many types of therapies. However, the regulatory mechanisms underlying CSC-specific properties, including self-renewal, are poorly understood. Here, we found that LATS1/2, the core Hippo pathway-kinases, were highly expressed in the oral squamous cell carcinoma line SAS, which exhibits high capacity of CSCs, and that depletion of these kinases prevented SAS cells from forming spheres under serum-free conditions. Detailed examination of the expression and activation of LATS kinases and related proteins over a time course of sphere formation revealed that LATS1/2 were more highly expressed and markedly activated before initiation of self-renewal. Moreover, TAZ, SNAIL, CHK1/2, and Aurora-A were expressed in hierarchical, oscillating patterns during sphere formation, suggesting that the process consists of four sequential steps. Our results indicate that LATS1/2 trigger self-renewal of CSCs by regulating the Hippo pathway, the EMT, and cell division.

References

Feb 20, 2007·Current Opinion in Cell Biology·Riccardo Fodde, Thomas Brabletz
May 5, 2007·The Journal of Biological Chemistry·Norikazu YabutaHiroshi Nojima
Aug 7, 2008·PloS One·Anne-Pierre MorelAlain Puisieux
Mar 20, 2010·Cellular and Molecular Life Sciences : CMLS·Gaoliang OuyangChaoyong James Yang
Oct 19, 2010·Developmental Cell·Duojia Pan
Dec 2, 2010·Journal of Cell Science·Nobuhiro OkadaHiroshi Nojima
Jan 8, 2011·Cell Stem Cell·Cedric BlanpainEmmanuelle Passegué
Dec 23, 2011·Genes & Development·Krishna P L BhatKenneth D Aldape
Aug 7, 2012·Cell Stem Cell·Dung-Fang LeeIhor R Lemischka
Dec 12, 2012·Journal of Cell Science·Norikazu YabutaHiroshi Nojima
Apr 4, 2013·Nature Cell Biology·Jan Paul Medema
May 7, 2013·Oral Oncology·M A González-MolesJ J Plaza-Campillo
Jul 28, 2013·Journal of Cell Science·Hirokazu SuzukiHiroshi Nojima
Sep 17, 2013·Journal of Cellular Physiology·Jin HaoZhihe Zhao
Sep 21, 2013·Nature·Corbin E Meacham, Sean J Morrison
Jan 15, 2014·Cell Death and Differentiation·Y AylonM Oren
Mar 13, 2014·Cell Stem Cell·Antonija Kreso, John E Dick
Feb 24, 2015·Trends in Molecular Medicine·Steven W PlouffeKun-Liang Guan
Mar 22, 2015·Molecular Cancer Research : MCR·Samantha E HiemerXaralabos Varelas
Apr 4, 2015·Nature Communications·Upal Basu-RoyClaudio Basilico

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Citations

Oct 6, 2019·Journal of Cancer Research and Clinical Oncology·Céline MontavonAndré Fedier

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