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

Masami Nozaki, Norikazu Yabuta, Moe Fukuzawa, Satomi Mukai, Ayumi Okamoto, Towa Sasakura, Kohshiro Fukushima, Yoko Naito, Gregory D. Longmore, Hiroshi Nojima

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Pages (from-to)1014-1030
Number of pages17
JournalOncotarget
Volume10
Issue number10
DOIs
StatePublished - Feb 1 2019

Keywords

  • Cancer stem cells (CSCs)
  • Hippo pathway
  • LATS
  • Oral cancer
  • SNAIL

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