Growth Hormone and the Epithelial-to-Mesenchymal Transition

Abstract

Our findings suggest that a myriad of molecular mechanisms are induced by GH that cause EMT and may point to potential therapeutic use of GH antagonists or any downregulator of GH action in EMT-related disease.

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

“…In fact, a chronic (3 week) treatment with GH alone increased the drug-resistance in human melanoma cells, increasing the EC50 values for vemurafenib and upregulating EMT(131). We also reported that GH upregulates the process of EMT in melanoma(130, 131) and refer the readers to our recent review of GH and EMT in cancer and normal tissues (167). The combination of the above results may help to define the mechanism(s) underlying development of drug resistance in several types of cancers overexpressing GHR and the earlier observations of GH-associated therapy resistance.…”

The effects of growth hormone on therapy resistance in cancer

“…A significant volume of research in vitro, in vivo, in clinical specimens and retrospective meta-analysis on human patients of GH-excess (acromegaly) and GH-resistance (LS) have established that a paracrine/ autocrine GH supports oncogenesis and drives neoplasms towards malignancy, metastasis or relapse in multiple tissues [2,3,63] . We refer our readers to a series of relevant reviews by us and colleagues in this regard, compiling the systematic comprehension of the overall and molecular details of how GHR-positive cancer cells exploit the versatile effects of GH action [2][3][4][64][65][66][67][68][69] . In relevance, the association between GH treatment and cancer incidence in GHD patients remains unclear and widely debated [70] .…”

“…Several different types of human cancers, including cancers of breast, colon, thyroid, blood, skin, pancreas, liver, endometrium, kidney, lung, stomach, glia, thymus, and brain express GHR [2] . In these cancers paracrine/autocrine GH induces oncogenic signaling for classical oncogenic processes like proliferation, migration, invasion, angiogenesis [87] , metastasis [65] , and avoiding apoptosis [88] . IGF1, one of the principal effectors of GH action, is also [89] important in progression of specific transformed cells and in driving therapy resistance in cancer [90] .…”

Excess growth hormone suppresses DNA damage repair in epithelial cells

“…Excess pituitary tumor GH secretion in acromegaly results in soft tissue overgrowth and increased adenoma formation in the colon, skin, thyroid, and prostate (21), and it is associated with increased risk for colorectal carcinoma (22,23). GH triggers epithelial-to-mesenchymal transition, creating a proneoplastic mucosal environment (24)(25)(26)(27). By contrast, abrogated GH signaling is associated with decreased cancer development in humans and in mice (20,(28)(29)(30).…”