| Literature DB >> 31352078 |
Ying Xiao1, Hui Zhang2, Qiang Ma2, Rui Huang2, Junliang Lu2, Xiaolong Liang2, Xuguang Liu2, Zhiwen Zhang2, Lianyuan Yu2, Junyi Pang2, Liangrui Zhou2, Tonghua Liu3, Huanwen Wu4, Zhiyong Liang5.
Abstract
Pancreatic stellate cells (PSCs) are activated in pancreatic ductal adenocarcinoma (PDAC) and are responsible for dense desmoplastic stroma. Yes-associated protein 1 (YAP1) can induce cancer-associated fibroblast activation in liver and breast tumors, but its effect on PSCs is unknown. In the present study, we determined that YAP1 was highly expressed in the nuclei of PDAC-derived activated PSCs. RNAi-mediated or pharmacological inhibition of YAP1 led to PSC deactivation. In addition, YAP1 stimulated the expression of secreted protein acidic and cysteine rich (SPARC) in PSCs, which was inhibited by RUNX1. SPARC secreted from PSCs inhibited pancreatic cancer cell (PCC) proliferation. High expression of nuclear YAP1 in tumor stroma was significantly correlated with SPARC expression and fibrosis degree in human PDAC tissues. Our study revealed a critical role for YAP1 in the regulation of PSC activation and paracrine signaling. Our findings provide insights into a novel rationale for targeting YAP1 to reprogram the PDAC microenvironment.Entities:
Keywords: Extracellular matrix; Pancreatic ductal adenocarcinoma; Pancreatic stellate cells; Secreted protein acidic and cysteine rich; Yes-associated protein 1
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Year: 2019 PMID： 31352078 DOI： 10.1016/j.canlet.2019.07.015
Source DB: PubMed Journal: Cancer Lett ISSN： 0304-3835 Impact factor: 8.679