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Title: Autocrine hGH stimulates oncogenicity, epithelial-mesenchymal transition and cancer stem cell-like behavior in human colorectal carcinoma
Authors: Wang J.-J. 
Chong Q.-Y. 
Sun X.-B.
You M.-L. 
Pandey V. 
Chen Y.-J. 
Zhuang Q.-S. 
Liu D.-X.
Ma L.
Wu Z.-S.
Zhu T.
Lobie P.E. 
Keywords: fibronectin
human growth hormone
mitogen activated protein kinase 1
mitogen activated protein kinase 3
autocrine effect
cancer growth
cancer stem cell
cell activation
cell function
cell proliferation
cell stimulation
cell survival
colorectal carcinoma
controlled study
disease association
drug targeting
enzyme inhibition
enzyme repression
epithelial mesenchymal transition
growth hormone release
human cell
human tissue
in vivo study
lymph node metastasis
major clinical study
metastatic colorectal cancer
middle aged
protein analysis
protein expression
therapy effect
tumor growth
tumor volume
Issue Date: 2017
Citation: Wang J.-J., Chong Q.-Y., Sun X.-B., You M.-L., Pandey V., Chen Y.-J., Zhuang Q.-S., Liu D.-X., Ma L., Wu Z.-S., Zhu T., Lobie P.E. (2017). Autocrine hGH stimulates oncogenicity, epithelial-mesenchymal transition and cancer stem cell-like behavior in human colorectal carcinoma. Oncotarget 8 (61) : 103900-103918. ScholarBank@NUS Repository.
Abstract: 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 hGHstimulated 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 hGHenhanced 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. © Wang et al.
Source Title: Oncotarget
ISSN: 19492553
DOI: 10.18632/oncotarget.21812
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