Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers.

Yunyun Cheng,Linlin Hao,Xue Wang,Jie Song,Ruirui Gui,Zhicheng Wang,Wanqiao Li,Chunli Wang,Yannan Shen,Zhaoguo Wang

doi:10.3389/fcell.2021.671247

Abstract

Radiotherapy remains one of the most important cancer treatment modalities. In the course of radiotherapy for tumor treatment, the incidental irradiation of adjacent tissues could not be completely avoided. DNA damage is one of the main factors of cell death caused by ionizing radiation, including single-strand (SSBs) and double-strand breaks (DSBs). The growth hormone-Insulin-like growth factor 1 (GH-IGF1) axis plays numerous roles in various systems by promoting cell proliferation and inhibiting apoptosis, supporting its effects in inducing the development of multiple cancers. Meanwhile, the GH-IGF1 signaling involved in DNA damage response (DDR) and DNA damage repair determines the radio-resistance of cancer cells subjected to radiotherapy and repair of adjacent tissues damaged by radiotherapy. In the present review, we firstly summarized the studies on GH-IGF1 signaling in the development of cancers. Then we discussed the adverse effect of GH-IGF1 signaling in radiotherapy to cancer cells and the favorable impact of GH-IGF1 signaling on radiation damage repair to adjacent tissues after irradiation. This review further summarized recent advances on research into the molecular mechanism of GH-IGF1 signaling pathway in these effects, expecting to specify the dual characters of GH-IGF1 signaling pathways in radiotherapy and post-radiotherapy repair of cancers, subsequently providing theoretical basis of their roles in increasing radiation sensitivity during cancer radiotherapy and repairing damage after radiotherapy.

Highlights

The growth hormone-insulin-like growth factors (GH-IGFs) growth axis plays widely roles in varieties of systems, including nervous system, reproductive system, skeletal system, muscular system, and immune system (Lu et al, 2019)
GH and IGF1 regulate the process by promoting cell proliferation through janus kinase 2/signal transducer and activator of transcription 5 (JAK2/STAT5) signaling pathway or phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase/extracellular regulated MAP kinase 1/2 (MAPK/ERK1/2) pathways, inducing homologous recombination (HR) or non-homologous end joining (NHEJ) to repair DNA damage and decreasing pro-apoptotic molecules (Bax, caspase3) (Valenciano et al, 2012; Basu and Kopchick, 2019)
We have summarized the resistance of GH and IGF1 signaling pathways to radiotherapy, which is not conducive to treatment, but a large number of studies have shown that they have recovery effect on the damage of adjacent tissues post-radiotherapy

Summary

INTRODUCTION

The growth hormone-insulin-like growth factors (GH-IGFs) growth axis plays widely roles in varieties of systems, including nervous system, reproductive system, skeletal system, muscular system, and immune system (Lu et al, 2019). IGF1 plays an essential role in the body growth, especially the postnatal life, and is involved in many cell processes, including cell proliferation, cell differentiation, and cell apoptosis through the IGF1 receptor (IGF1R) and the subsequent activation of MAPK/ERK1/2 and PI3K/Akt signaling pathways (Yamauchi and Pessin, 1994; Grey et al, 2003). Individuals with GHR deficiency (GHRD) caused by genetic mutations in the displayed GHR gene and congenital IGF1 appear to be protected against the development of neoplasms This protection, well documented, is not absolute in IGHD, GHD associated with multiple pituitary defects and GHRH receptor deficiency (Shevah and Laron, 2007; Guevara-Aguirre et al, 2011; Steuerman et al, 2011; Marinho et al, 2018)

Role of GH Signaling in Cancers

Effects of GH Signaling on Therapy Resistance in Cancer Radiotherapy

Findings

AUTHOR CONTRIBUTIONS