Journal
STEM CELLS
Volume 40, Issue 2, Pages 165-174Publisher
OXFORD UNIV PRESS
DOI: 10.1093/stmcls/sxab019
Keywords
adult stem cells; cell adhesion molecules; cell biology; cellular proliferation; mesenchymal stem cells (MSCs); proliferation
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Funding
- AO Foundation, Switzerland [S-14-29L]
- Dutch Province of Limburg
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Cadherin-11 regulates the activity of RTKs in hMSCs, affecting the activation of the MAPK pathway and cell proliferation.
Controlling stem cell fate is the cornerstone of regenerative medicine. Cadherins have an important role in cell fate commitment and the function of cadherin-11 in the regulation of differentiation in human mesenchymal stem cells (hMSCs) has recently come to light. To better understand how cadherin-11 regulates hMSC behavior, we explored its interaction with receptor tyrosine kinases (RTK), an important family of proteins involved in a myriad of cellular functions. In this study, we provide evidence that cadherin-11, a cell adhesion protein expressed in hMSCs, regulates the activity of several RTKs, including PDGFR beta and PDGFR alpha. By knocking down cadherin-11 we found that the changes in the RTK activity caused hyperactivation of the MAPK pathways, which were sustained through the phosphorylation and nuclear translocation of ERK1/2 and subsequently caused a decrease in cell proliferation. Together these results provide compelling evidence for the important role of the interaction of cadherin-11 and RTKs in the behavior of hMSCs.
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