FAM198B is associated with prolonged survival and inhibits metastasis in lung adenocarcinoma via blockage of ERK-Mediated MMP-1 expression

Chia Ying Hsu, Gee Chen Chang, Yi Ju Chen, Yi Chiung Hsu, Yi Jing Hsiao, Kang Yi Su, Hsuan Yu Chen, Chien Yu Lin, Jin Shing Chen, Yu Ju Chen, Qi Sheng Hong, Wen Hui Ku, Chih Ying Wu, Bing Ching Ho, Ching Cheng Chiang, Pan Chyr Yang, Sung Liang Yu

研究成果: 雜誌貢獻期刊論文同行評審

21 引文 斯高帕斯(Scopus)


Purpose: The comprehensive understanding of mechanisms involved in the tumor metastasis is urgently needed for discovering novel metastasis-related genes for developing effective diagnoses and treatments for lung cancer. Experimental Design: FAM198B was identified from an isogenic lung cancer metastasis cell model by microarray analysis. To investigate the clinical relevance of FAM198B, the FAM198B expression of 95 Taiwan lung adenocarcinoma patients was analyzed by quantitative real-time PCR and correlated to patients' survivals. The impact of FAM198B on cell invasion, metastasis, and tumor growth was examined by in vitro cellular assays and in vivo mouse models. In addition, the N-glycosylation–defective FAM198B mutants generated by site-directed mutagenesis were used to study protein stability and subcellular localization of FAM198B. Finally, the microarray and pathway analyses were used to elucidate the underlying mechanisms of FAM198B-mediated tumor suppression. Results: We found that the high expression of FAM198B was associated with favorable survival in Taiwan lung adenocarcinoma patients and in a lung cancer public database. Enforced expression of FAM198B inhibited cell invasion, migration, mobility, proliferation, and anchorage-independent growth, and FAM198B silencing exhibited opposite activities in vitro. FAM198B also attenuated tumor growth and metastasis in vivo. We further identified MMP-1 as a critical downstream target of FAM198B. The FAM198B-mediated MMP-1 downregulation was via inhibition of the phosphorylation of ERK. Interestingly deglycosylation nearly eliminated the metastasis suppression activity of FAM198B due to a decrease of protein stability. Conclusions: Our results implicate FAM198B as a potential tumor suppressor and to be a prognostic marker in lung adenocarcinoma.

頁(從 - 到)916-926
期刊Clinical Cancer Research
出版狀態已出版 - 15 2月 2018


深入研究「FAM198B is associated with prolonged survival and inhibits metastasis in lung adenocarcinoma via blockage of ERK-Mediated MMP-1 expression」主題。共同形成了獨特的指紋。