Growth Hormone Receptor Regulation in Cancer and Chronic Diseases

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2020 Dec 14

PMID 33312162

Citations 26

Authors

Ger J Strous

Ana Da Silva Almeida

Joyce Putters

Julia Schantl

Magdalena Sedek

Johan A Slotman

Tobias Nespital

Gerco C Hassink

Jan A Mol

Affiliations

Soon will be listed here.

Abstract

The GHR signaling pathway plays important roles in growth, metabolism, cell cycle control, immunity, homeostatic processes, and chemoresistance both the JAK/STAT and the SRC pathways. Dysregulation of GHR signaling is associated with various diseases and chronic conditions such as acromegaly, cancer, aging, metabolic disease, fibroses, inflammation and autoimmunity. Numerous studies entailing the GHR signaling pathway have been conducted for various cancers. Diverse factors mediate the up- or down-regulation of GHR signaling through post-translational modifications. Of the numerous modifications, ubiquitination and deubiquitination are prominent events. Ubiquitination by E3 ligase attaches ubiquitins to target proteins and induces proteasomal degradation or starts the sequence of events that leads to endocytosis and lysosomal degradation. In this review, we discuss the role of first line effectors that act directly on the GHR at the cell surface including ADAM17, JAK2, SRC family member Lyn, Ubc13/CHIP, proteasome, βTrCP, CK2, STAT5b, and SOCS2. Activity of all, except JAK2, Lyn and STAT5b, counteract GHR signaling. Loss of their function increases the GH-induced signaling in favor of aging and certain chronic diseases, exemplified by increased lung cancer risk in case of a mutation in the SOCS2-GHR interaction site. Insight in their roles in GHR signaling can be applied for cancer and other therapeutic strategies.

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