https://scholars.lib.ntu.edu.tw/handle/123456789/480998
Title: | FAM198B is associated with prolonged survival and inhibits metastasis in lung adenocarcinoma via blockage of ERK-Mediated MMP-1 expression | Authors: | Hsu C.-Y. Chang G.-C. Chen Y.-J. Hsu Y.-C. Hsiao Y.-J. KANG-YI SU Chen H.-Y. Lin C.-Y. JIN-SHING CHEN Chen Y.-J. Hong Q.-S. Ku W.-H. Wu C.-Y. Ho B.-C. Chiang C.-C. PAN-CHYR YANG SUNG-LIANG YU |
Issue Date: | 2018 | Publisher: | American Association for Cancer Research Inc. | Journal Volume: | 24 | Journal Issue: | 4 | Start page/Pages: | 916-926 | Source: | Clinical Cancer Research | Abstract: | 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. ? 2017 American Association for Cancer Research. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85042230149&doi=10.1158%2f1078-0432.CCR-17-1347&partnerID=40&md5=61d5b30153397be38f8a4674b6abb354 https://scholars.lib.ntu.edu.tw/handle/123456789/480998 |
ISSN: | 1078-0432 | DOI: | 10.1158/1078-0432.CCR-17-1347 | SDG/Keyword: | FAM198B protein; interstitial collagenase; mitogen activated protein kinase; mutant protein; tumor suppressor protein; unclassified drug; interstitial collagenase; membrane protein; mitogen activated protein kinase; anchorage independent growth; animal cell; animal experiment; animal model; animal tissue; Article; cancer cell; cancer inhibition; cancer model; cancer prognosis; cancer survival; cell invasion; cell migration; cell motility; cell proliferation; cellular distribution; controlled study; deglycosylation; diagnostic test accuracy study; down regulation; enzyme activity; enzyme inhibition; enzyme phosphorylation; FAM198B gene; gene activity; gene expression; gene silencing; gene targeting; genetic association; human; human tissue; in vitro study; in vivo study; lung adenocarcinoma; metastasis inhibition; microarray analysis; mouse; nonhuman; priority journal; protein defect; protein expression; protein glycosylation; protein localization; protein protein interaction; protein stability; protein targeting; reference value; site directed mutagenesis; survival time; Taiwan; tumor suppressor gene; adenocarcinoma; animal; Asian continental ancestry group; DNA microarray; ethnology; gene expression regulation; genetics; Kaplan Meier method; lung tumor; metabolism; metastasis; procedures; RNA interference; SCID mouse; tumor cell line; tumor volume; xenograft; Adenocarcinoma; Animals; Asian Continental Ancestry Group; Cell Line, Tumor; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Matrix Metalloproteinase 1; Membrane Glycoproteins; Mice, SCID; Neoplasm Metastasis; Oligonucleotide Array Sequence Analysis; RNA Interference; Taiwan; Transplantation, Heterologous; Tumor Burden |
Appears in Collections: | 醫學系 |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.