Paracrine HGF/c-MET enhances the stem cell-like potential and glycolysis of pancreatic cancer cells via activation of YAP/HIF-1α
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061 (China)
Highlights: • c-MET mediates the role of paracrine HGF in pancreatic cancer cell stemness. • HGF/c-MET modulates the Warburg effect in pancreatic cancer cells. • HGF/c-MET targets YAP and regulates YAP downstream targets. • HGF/c-MET/YAP/HIF-1α signaling may modulate tumor metabostemness. Pancreatic stellate cells (PSCs), a pivotal component of the tumor microenvironment, contribute to tumor growth and metastasis. PSC-derived factors are essential for triggering the generation and maintenance of cancer stem cells (CSCs). However, the mechanisms by which paracrine signals regulate CSC-like properties such as glycolytic metabolism have not been fully elucidated. Here, we report that two pancreatic cancer cell lines, Panc-1 and MiaPaCa-2, reacted differently when treated with hepatocyte growth factor (HGF) secreted from PSCs. MiaPaCa-2 cells showed little response with regard to CSC-like properties after HGF treatment. We have shown that in Panc-1 cells by activating its cognate receptor c-MET, paracrine HGF resulted in YAP nuclear translocation and HIF-1α stabilization, thereby promoting the expression of CSC pluripotency markers NANOG, OCT-4 and SOX-2 and tumor sphere formation ability. Furthermore, HGF/c-MET/YAP/HIF-1α signaling enhanced the expression of Hexokinase 2 (HK2) and promoted glycolytic metabolism, which may facilitate CSC-like properties. Collectively, our study demonstrated that HGF/c-MET modulates tumor metabostemness by regulating YAP/HIF-1α and may hold promise as a potential therapeutic target against pancreatic cancer.
- OSTI ID:
- 23082594
- Journal Information:
- Experimental Cell Research, Vol. 371, Issue 1; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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