Background
Tumor chemo-resistance is a hallmark of malignant tumors as well as the major cause of poor survival rates in lung cancer.
Transmembrane-4 L-six family member-1 (TM4SF1)
, an antigen that serves as an oncogene, mainly affects tumor invasion and metastasis. We investigated the roles of
TM4SF1
in non-small-cell lung cancer progression, particularly in the regulation of chemo-sensitivity.
Methods
TM4SF1
was silenced by small interfering RNA transfection.
TM4SF1
expression in cell lines and tissues were determined by Quantitative Real-time PCR. MTS, clonogenic, Transwell assay, Flow cytometry verified cell function. By RT-PCR, Western blot, the mechanisms were studied.
Results
TM4SF1
was upregulated in both lung cancer cell lines and tissues, compared with 293 T epithelial cells. Analysis of online databases revealed that high expression of
TM4SF1
is associated with the older patient age, smoking habits, and poor patient survival and outcome. Knockdown of
TM4SF1
substantially inhibited tumor cell growth, migration, and invasion, and enhanced the chemo-sensitivity of the lung cancer cell lines A549 and H1299 to cisplatin and paclitaxel. Furthermore, the silencing of
TM4SF1
induced lung cancer cell apoptosis and arrested cells at the G2/M phase. These results suggest that
TM4SF1
is associated with lung cancer progression and appears to be required for tumor cell growth, maintenance of chemo-resistance and metastasis. We further found that TM4SF1 exerts these effects in part by regulating the expression of the discoidin domain receptor DDR1 and its downstream target, the Akt/ERK/mTOR pathway, and consequently alters cell sensitivity to chemo-reagents and contributes to invasion and metastasis.
Conclusions
These findings demonstrate that TM4SF1 may serve as a prognostic factor for lung cancer chemo-response and patient outcome.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.