TMEM176B Promotes EMT via FGFR/JNK Signalling in Development and Tumourigenesis of Lung Adenocarcinoma

Sun, Ping-Hui1,2,3; Xia, Siyu4; Yuan, Runzhu5; Zhang, Bin1; Wang, Guangsuo1

2024-07-01

10.3390/cancers16132447

CANCERS   影响因子和分区

2072-6694

Simple Summary TMEM176B has been reported to play a significant role in the regulation of dendritic cell maturation and other immune functions. Additionally, TMEM176B has been implicated in the development of various cancers, including breast cancer and colorectal cancer, where its expression levels correlate with disease progression and patient outcomes. This study aims to investigate the role of TMEM176B in the development of lung adenocarcinoma (LUAD). Our research indicates that the overexpression of TMEM176B is associated with a poor prognosis in LUAD patients, signifying more aggressive disease and reduced survival rates. Moreover, we have found that TMEM176B overexpression enhances the epithelial-mesenchymal transition (EMT) via the FGFR/JNK signalling pathway. This pathway is integral to cell growth, differentiation, and survival and its dysregulation can contribute to tumour progression and metastasis. These findings suggest that TMEM176B could serve as a potential therapeutic target for LUAD treatment, offering new avenues for developing targeted therapies.Abstract Lung cancer, the leading cause of cancer-related incidence and mortality worldwide, is characterised by high invasiveness and poor prognosis. Novel therapeutic targets are required, especially for patients with inoperable metastatic disease requiring systemic therapies to improve patients' welfare. Recently, studies indicated that TMEM176B is a positive regulator in breast and gastric cancers, and it could be a potential target for treatment. In this study, we used single-cell sequencing, proteomics, Co-IP, and in vivo and in vitro experimental models to investigate the role of TMEM176B in lung adenocarcinoma development. Our study indicated that TMEM176B expression was enhanced in lung adenocarcinoma tissues, and it was associated with shorter overall survival (OS). TMEM176B promoted cellular functions, including cell proliferation, invasion, migration and adhesion in vitro and tumour growth in vivo. Moreover, the tube formation ability of endothelial cells was enhanced by treating with the tumour cell-conditioned medium. We have also demonstrated that TMEM176B regulated EMT via the FGFR1/JNK/Vimentin/Snail signalling cascade. Overall, our study suggests TMEM176B could be a potential therapeutic target in lung adenocarcinoma.

lung cancer TMEM176B EMT cellular microenvironment single-cell sequence proteomics

SCI

英语

其他

Shenzhen Science and Technology Innovation Committee[JCYJ20220530152810023] ; National Natural Science Foundation of China[82201786] ; Guangdong Basic and Applied Basic Research Foundation[2021A1515110646] ; Shenzhen-Hong Kong-Macau Science and Technology Programme[SGDX20220530111201008] ; Shenzhen People's Hospital Clinical Scientist Programme[SYWGSCGZH202305]

Oncology

Oncology

WOS:001269796600001

MDPI

Web of Science

1.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Thorac Surg, Shenzhen 518000, Peoples R China
2.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Res, Guangzhou 510632, Peoples R China
3.Cardiff Univ, Sch Med, Div Canc & Genet, Cardiff CF14 4XN, Wales
4.Dongguan Maternal & Child Hlth Care Hosp, Dept Reprod Med, Dongguan 523000, Peoples R China
5.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Sch Med, Shenzhen 518000, Peoples R China

Sun, Ping-Hui,Xia, Siyu,Yuan, Runzhu,et al. TMEM176B Promotes EMT via FGFR/JNK Signalling in Development and Tumourigenesis of Lung Adenocarcinoma[J]. CANCERS,2024,16(13).

Sun, Ping-Hui,Xia, Siyu,Yuan, Runzhu,Zhang, Bin,&Wang, Guangsuo.(2024).TMEM176B Promotes EMT via FGFR/JNK Signalling in Development and Tumourigenesis of Lung Adenocarcinoma.CANCERS,16(13).

Sun, Ping-Hui,et al."TMEM176B Promotes EMT via FGFR/JNK Signalling in Development and Tumourigenesis of Lung Adenocarcinoma".CANCERS 16.13(2024).