Hippo signaling controls cell cycle and restricts cell plasticity in planarians

PLoS Biol. 2018 Jan 22;16(1):e2002399. doi: 10.1371/journal.pbio.2002399. eCollection 2018 Jan.

Abstract

The Hippo pathway plays a key role in regulating cell turnover in adult tissues, and abnormalities in this pathway are consistently associated with human cancers. Hippo was initially implicated in the control of cell proliferation and death, and its inhibition is linked to the expansion of stem cells and progenitors, leading to larger organ size and tumor formation. To understand the mechanism by which Hippo directs cell renewal and promotes stemness, we studied its function in planarians. These stem cell-based organisms are ideal models for the analysis of the complex cellular events underlying tissue renewal in the whole organism. hippo RNA interference (RNAi) in planarians decreased apoptotic cell death, induced cell cycle arrest, and could promote the dedifferentiation of postmitotic cells. hippo RNAi resulted in extensive undifferentiated areas and overgrowths, with no effect on body size or cell number. We propose an essential role for hippo in controlling cell cycle, restricting cell plasticity, and thereby preventing tumoral transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle / physiology
  • Cell Differentiation
  • Cell Division
  • Cell Plasticity / physiology*
  • Cell Proliferation
  • Planarians / metabolism
  • Planarians / physiology
  • Protein-Serine-Threonine Kinases / physiology*
  • RNA Interference
  • Signal Transduction
  • Stem Cells / physiology

Substances

  • Hippo protein, human
  • Protein-Serine-Threonine Kinases

Grant support

Universitat de Barcelona (APIF fellowship). Received by NdS. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Ministerio de educación y ciencia (grant number BFU2017-83755-P and BFU2014-56055-P). Received by ES and TA. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. AGAUR (Generalitat de Catalunya) (grant number 2009SGR1018). Received by ES. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.