Open AccessTMEM139 prevents NSCLC metastasis by inhibiting lysosomal degradation of E‐cadherin
Author(s) -
Zhang Shuai,
He Yunlong,
Xuan Qijia,
Ling Xiaodong,
Men Kaiya,
Zhao Xu,
Xue Dinglong,
Li Ling,
Zhang Yingying
Publication year - 2022
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15341
Subject(s) - metastasis , cadherin , cancer research , lung cancer , epithelial–mesenchymal transition , in vitro , transmembrane protein , cancer , medicine , oncology , biology , cell , biochemistry , receptor
Non‐small‐cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and has the highest mortality rate among all solid tumors. It is characterized by early metastasis, and investigations of the molecular mechanisms underlying the progression and metastasis of NSCLC are urgently needed for the development of therapeutic targets. Here, we report that the transmembrane protein TMEM139 is significantly downregulated in NSCLC and that reduced expression of TMEM139 is correlated with a poor prognosis in NSCLC patients. Mechanistically, we found that TMEM139 directly interacts with E‐cadherin at the plasma membrane and at focal adhesion sites. Moreover, TMEM139 can prevent the lysosomal degradation of E‐cadherin, which inhibits epithelial‐mesenchymal transition, migration and invasion of NSCLC cells both in vitro and in vivo. Our study not only expands our understanding of NSCLC metastasis but also provides a foundation to develop novel therapeutic strategies.