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

Jing Jing Wang, Qing Yun Chong, Xin Bao Sun, Ming Liang You, Vijay Pandey, Yi Jun Chen, Qiu Shi Zhuang, Dong Xu Liu, Lan Ma, Zheng Sheng Wu, Tao Zhu, Peter E. Lobie

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)103900-103918
Number of pages19
JournalOncotarget
Volume8
Issue number61
DOIs
StatePublished - 2017

Keywords

  • Cancer stem cell
  • Colorectal carcinoma
  • ERK
  • Epithelial-mesenchymal transition
  • Growth hormone

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Autocrine hGH stimulates oncogenicity, epithelial-mesenchymal transition and cancer stem cell-like behavior in human colorectal carcinoma'. Together they form a unique fingerprint.

Cite this