PMID- 35052826 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220128 IS - 2227-9059 (Print) IS - 2227-9059 (Electronic) IS - 2227-9059 (Linking) VI - 10 IP - 1 DP - 2022 Jan 11 TI - Distinctive Roles of YAP and TAZ in Human Endothelial Progenitor Cells Growth and Functions. LID - 10.3390/biomedicines10010147 [doi] LID - 147 AB - The hippo signaling pathway plays an essential role in controlling organ size and balancing tissue homeostasis. Its two main effectors, yes-associated protein (YAP) and WW domain-containing transcription regulator 1, WWTR1 or TAZ, have also been shown to regulate endothelial cell functions and angiogenesis. In this study, the functions of YAP and TAZ in human endothelial progenitor cells (EPCs) were investigated by a loss-of-function study using CRISPR/Cas9-mediated gene knockdown (KD). Depletion of either YAP or TAZ reduced EPC survival and impaired many of their critical functions, including migration, invasion, vessel-formation, and expression of pro-angiogenic genes. Notably, TAZ-KD EPCs exhibited more severe phenotypes in comparison to YAP-KD EPCs. Moreover, the conditioned medium derived from TAZ-KD EPCs reduced the survivability of human lung cancer cells and increased their sensitivity to chemotherapeutic agents. The overexpression of either wild-type or constitutively active TAZ rescued the impaired phenotypes of TAZ-KD EPCs and restored the expression of pro-angiogenic genes in those EPCs. In summary, we demonstrate the crucial role of Hippo signaling components, YAP and TAZ, in controlling several aspects of EPC functions that can potentially be used as a drug target to enhance EPC functions in patients. FAU - Klaihmon, Phatchanat AU - Klaihmon P AD - Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. FAU - Lorthongpanich, Chanchao AU - Lorthongpanich C AD - Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. FAU - Kheolamai, Pakpoom AU - Kheolamai P AD - Center of Excellence in Stem Cell Research and Innovation, Faculty of Medicine, Thammasat University, Pathum Thani 12120, Thailand. FAU - Luanpitpong, Sudjit AU - Luanpitpong S AUID- ORCID: 0000-0002-1639-4935 AD - Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. FAU - Issaragrisil, Surapol AU - Issaragrisil S AD - Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. LA - eng GR - N41A640154/National Research Council of Thailand/ GR - N41A640122/National Research Council of Thailand/ GR - D003276/Siriraj Foundation for Stem Cell Research/ PT - Journal Article DEP - 20220111 PL - Switzerland TA - Biomedicines JT - Biomedicines JID - 101691304 PMC - PMC8773510 OTO - NOTNLM OT - YAP/TAZ OT - endothelial progenitor cells OT - hippo signaling pathway COIS- The authors declare no potential conflicts of interest. EDAT- 2022/01/22 06:00 MHDA- 2022/01/22 06:01 PMCR- 2022/01/11 CRDT- 2022/01/21 01:03 PHST- 2021/11/04 00:00 [received] PHST- 2022/01/04 00:00 [revised] PHST- 2022/01/04 00:00 [accepted] PHST- 2022/01/21 01:03 [entrez] PHST- 2022/01/22 06:00 [pubmed] PHST- 2022/01/22 06:01 [medline] PHST- 2022/01/11 00:00 [pmc-release] AID - biomedicines10010147 [pii] AID - biomedicines-10-00147 [pii] AID - 10.3390/biomedicines10010147 [doi] PST - epublish SO - Biomedicines. 2022 Jan 11;10(1):147. doi: 10.3390/biomedicines10010147.