Autocrine hGH stimulates oncogenicity, epithelial-mesenchymal transition and cancer stem cell-like behavior in human colorectal carcinoma.

Autor:	Wang JJ; Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore, Singapore., Chong QY; Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore, Singapore., Sun XB; Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China.; The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, China., You ML; Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore, Singapore., Pandey V; Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore, Singapore., Chen YJ; Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore, Singapore., Zhuang QS; Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore, Singapore., Liu DX; School of Science, Auckland University of Technology, Auckland, New Zealand., Ma L; Tsinghua Berkeley Shenzhen Institute, Tsinghua University Graduate School at Shenzhen, Shenzhen, China., Wu ZS; Department of Pathology, Anhui Medical University, Hefei, China., Zhu T; Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China.; The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, China., Lobie PE; Cancer Science Institute of Singapore and Department of Pharmacology, National University of Singapore, Singapore, Singapore.; Tsinghua Berkeley Shenzhen Institute, Tsinghua University Graduate School at Shenzhen, Shenzhen, China.; National University Cancer Institute, Singapore, Singapore.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2017 Oct 10; Vol. 8 (61), pp. 103900-103918. Date of Electronic Publication: 2017 Oct 10 (Print Publication: 2017).
DOI:	10.18632/oncotarget.21812
Abstrakt:	Tumor derived human growth hormone (hGH) has been implicated in cancer development and progression. However, the specific functional role of autocrine/paracrine hGH in colorectal cancer (CRC) remains largely to be determined. Herein, we demonstrated a crucial oncogenic role of autocrine hGH in CRC progression. Elevated hGH expression was detected in CRC compared to normal colorectal tissue, and hGH expression in CRC was positively associated with tumor size and lymph node metastasis. Forced expression of hGH stimulated cell proliferation, survival, oncogenicity and epithelial to mesenchymal transition (EMT) of CRC cells, and promoted xenograft growth and local invasion in vivo . Autocrine hGH expression in CRC cells stimulated the activation of the ERK1/2 pathway, which in turn resulted in increased transcription of the mesenchymal marker FIBRONECTIN 1 and transcriptional repression of the epithelial marker E-CADHERIN. The autocrine hGH-stimulated increase in CRC cell proliferation, cell survival and EMT was abrogated upon ERK1/2 inhibition. Furthermore, autocrine hGH-stimulated CRC cell migration and invasion was dependent on the ERK1/2-mediated increase in FIBRONECTIN 1 expression and decrease in E-CADHERIN expression. Forced expression of hGH also enhanced CSC-like behavior of CRC cells, as characterized by increased colonosphere formation, ALDH-positive population and CSC marker expression. Autocrine hGH-enhanced cancer stem cell (CSC)-like behavior in CRC cells was also observed to be E-CADHERIN-dependent. Thus, autocrine hGH plays a critical role in CRC progression, and inhibition of hGH could be a promising targeted therapeutic approach to limit disease progression in metastatic CRC patients. Competing Interests: CONFLICTS OF INTEREST PEL and TZ have previously consulted for Perseis Therapeutics Ltd. PEL and TZ have direct or indirect equity interest in Wuhan Long Ke Ltd., a company which holds Chinese patent 20130446539.5. PEL is also named on PCT application numbers WO 2006/69253, WO/2008/042435, WO/2009/147530 and WO/2012/150869 and derivatives/national phase components of these applications thereof. JJW, QYC, XBS, MLY, VP, YJC, ZQS, DXL, LM and ZSW declare no conflict of interest.
Databáze:	MEDLINE
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