Tumor-associated Macrophages Promote Tumor Metastasis Via the TGF-β/SOX9 Axis in Non-small Cell Lung Cancer

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Dec 17

PMID 29245941

Citations 63

Authors

Shuai Zhang

Dehai Che

Fang Yang

Chunling Chi

Hongxue Meng

Jing Shen

Li Qi

Fang Liu

Liyan Lv

Yue Li

Qingwei Meng

Junning Liu

Lihua Shang

Yan Yu

Affiliations

Soon will be listed here.

Abstract

Tumor-associated macrophages (TAMs), most of which display the immunosuppressive M2 phenotype, affect the tumor microenvironment and promote progression and metastasis in lung carcinoma. In this study, we analyzed clinical non-small cell lung cancer (NSCLC) samples and found that high densities of TAMs were associated with a poor prognosis in NSCLC patients. Moreover, the number of TAMs present correlated positively with expression of sex determining region Y (SRY)-related high mobility group box 9 (SOX9) in NSCLC tissues. TAMs secreted TGF-β, which increased SOX9 expression and promoted epithelial-to-mesenchymal transition (EMT) in lung cancer cells, thereby promoting tumor proliferation, migration, and invasion. SOX9 knockdown inhibited EMT, indicating that TGF-β-mediated EMT is SOX9-dependent. TGF-β induced SOX9 expression by upregulating the C-jun/SMAD3 pathway. These results indicate that TGF-β secreted by TAMs promotes SOX9 expression via the C-jun/SMAD3 pathway, thereby promoting tumor metastasis. The TGF-β/SOX9 axis may therefore be an effective target for the treatment of lung cancer.

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