Suppressor of Cytokine Signalling-2 Limits IGF1R-mediated Regulation of Epithelial-mesenchymal Transition in Lung Adenocarcinoma

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2018 Mar 22

PMID 29559623

Citations 17

Authors

Yue Zhou

Zhilei Zhang

Ning Wang

Jizheng Chen

Xu Zhang

Min Guo

Li John Zhong

Qian Wang

Affiliations

Soon will be listed here.

Abstract

Non-small cell lung cancer (NSCLC), including adenocarcinoma and squamous cell carcinoma, is the leading cause of death from lung malignancies and has a poor prognosis due to metastasis. Suppressor of cytokine signalling-2 (SOCS2), a feedback inhibitor of cytokine signalling, has been shown to be involved in growth control. Here, we show that SOCS2 were significantly downregulated in tumour foci in NSCLC patients. The expression levels of SOCS2 significantly correlated with clinical stage, lymph node metastasis, histological subtype and survival time. In particular, the decreased expression of SOCS2 significantly associated with advanced pathological stage, lymph node metastasis and shorter overall survival in lung adenocarcinoma patients. In vivo animal results showed that overexpressed SOCS2 attenuated the metastatic characteristics of lung adenocarcinoma, including by inhibiting the epithelial-mesenchymal transition (EMT). Further functional studies indicated that insulin-like growth factor 1 (IGF1)-driven migratory and invasive behaviours of lung adenocarcinoma cells can be partially suppressed by exogenous SOCS2 expression. Investigations into the mechanism of action revealed that SOCS2 inhibits EMT by inactivating signal transducer and activator of transcription 3 (STAT3) and STAT5 via the competitive binding of SOCS2 to the STAT binding sites on IGF1R. Altogether, our results reveal an important role for SOCS2 dysregulation in the pathogenicity of lung adenocarcinoma, suggest its potential use as a biomarker for diagnosing lung adenocarcinoma, and paves the way to develop novel therapy targets as the axis of SOCS2-IGF1R-STAT in lung adenocarcinoma.

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