Title:Hippo Signaling: A Stress Response Pathway in Stem Cells
Volume: 16
Issue: 7
Author(s): Naciye Dilara Zeybek*, Eylem Baysal, Ozlem Bozdemir and Esra Buber
Affiliation:
- Department of Histology and Embryology, Faculty of Medicine, Hacettepe University, Ankara,Turkey
Keywords:
Hippo pathway, YAP/TAZ, stress, stem cell, oxidative stress, hypoxia, autophagy.
Abstract: The Hippo pathway, with its core components and the downstream transcriptional coactivators,
controls the self-renewable capacity and stemness features of stem cells and serves as a stress
response pathway by regulating proliferation, differentiation and apoptosis. The Hippo pathway interaction
with other signaling pathways plays an important role in response to various stress stimuli arising
from energy metabolism, hypoxia, reactive oxygen species, and mechanical forces. Depending on
the energy levels, the Hippo pathway is regulated by AMP-activated protein kinase (AMPK) and
mechanistic target of rapamycin (mTOR), which in turn determines stem cell proliferation (cell survival
and growth) and differentiation. Oxidative stress-driven by ROS production also affects the
Hippo pathway with transcriptional changes through MST/YAP/FoxO pathway and leads to the activation
of pro-apoptotic genes and eventually cell death. HIF1alpha/YAP signaling is critical for the
long-term maintenance of mesenchymal stem cells (MSCs) under hypoxia. In this review, we present
an overview of stem cell response to stress, including mechanical, hypoxia, metabolic and oxidative
stress through the modulation of the Hippo pathway. The biological effects such as autophagy, apoptosis
and senescence were discussed in the context of the Hippo pathway in stem cells.
