Oncogenic K-RasG12V cannot overcome proliferation failure caused by loss of Ppp6c in mouse embryonic fibroblasts

FEBS Open Bio. 2024 Apr;14(4):545-554. doi: 10.1002/2211-5463.13775. Epub 2024 Feb 6.

Abstract

Protein phosphatase 6 is a Ser/Thr protein phosphatase and its catalytic subunit is Ppp6c. Ppp6c is thought to be indispensable for proper growth of normal cells. On the other hand, loss of Ppp6c accelerates growth of oncogenic Ras-expressing cells. Although it has been studied in multiple contexts, the role(s) of Ppp6c in cell proliferation remains controversial. It is unclear how oncogenic K-Ras overcomes cell proliferation failure induced by Ppp6c deficiency; therefore, in this study, we attempted to shed light on how oncogenic K-Ras modulates tumor cell growth. Contrary to our expectations, loss of Ppp6c decreased proliferation, anchorage-independent growth in soft agar, and tumor formation of oncogenic Ras-expressing mouse embryonic fibroblasts (MEFs). These findings show that oncogenic K-RasG12V cannot overcome proliferation failure caused by loss of Ppp6c in MEFs.

Keywords: K‐RasG12V; MEF; PP6; Ppp6c; cell proliferation; tumor formation.

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Fibroblasts* / metabolism
  • Mice
  • Phosphoprotein Phosphatases* / genetics
  • Phosphoprotein Phosphatases* / metabolism
  • Proto-Oncogene Proteins p21(ras)* / genetics
  • Proto-Oncogene Proteins p21(ras)* / metabolism

Substances

  • Phosphoprotein Phosphatases
  • protein phosphatase 6
  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)