IGFBP7 Inhibits Cell Proliferation by Suppressing AKT Activity and Cell Cycle Progression in Thyroid Carcinoma

Overview

Journal Cell Biosci

Publisher Biomed Central

Specialty Biology

Date 2019 Jun 12

PMID 31183073

Citations 21

Authors

Le Zhang

Rong Lian

Jingjing Zhao

Xianming Feng

Runyi Ye

Lingxiao Pan

Jueheng Wu

Mengfeng Li

Yongbo Huan

Junchao Cai

Affiliations

Soon will be listed here.

Abstract

Background: Thyroid cancer is the most common malignant endocrine tumor and is classified into papillary thyroid cancer (PTC), follicular thyroid cancer (FTC) and anaplastic thyroid cancer (ATC), which have substantially different characteristics. Insulin-like growth factor binding protein 7 (IGFBP7) has recently been recognized as a tumor suppressor in many cancer types. However, the expression pattern of IGFBP7 and its biological function in various types of thyroid carcinoma remain poorly understood.

Results: We found that the protein levels of IGFBP7 in FTC and ATC tissues were significantly lower or even absent compared with those in normal thyroid, benign thyroid adenoma and classical PTC tissues. Moreover, overexpression of IGFBP7 in two undifferentiated ATC cell lines, ARO and FRO, and one differentiated FTC cell line, WRO, significantly inhibited cell proliferation in vitro. In vivo experiments revealed that ectopic IGFBP7 expression markedly suppressed growth of tumor xenografts derived from these thyroid cancer cell lines, while IGFBP7 silencing accelerated tumor growth. At the mechanistic level, overexpression of IGFBP7 dramatically suppressed phosphorylation-mediated activation and kinase activity of AKT, causing an upregulation of cyclin-dependent kinase (CDK) inhibitors p27 and p21 and induction of G1/S cell cycle arrest, while silencing IGFBP7 exerted the opposite effects.

Conclusions: IGFBP7 expression is decreased or even absent in FTC and ATC. Acting as a cell cycle repressor, IGFBP7 plays an important tumor-suppressive role in human thyroid cancer, especially in FTC and ATC subtypes and may represent a promising biomarker and therapeutic target for human thyroid cancer treatment.

Citing Articles

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