經歷

國立陽明大學 醫師科學家學程 負責人
國立陽明大學 生化暨分子生物研究所 副教授

榮譽

指導學生獲獎

研究方向

癌症進展之分子機制; 癌細胞移行與癌症侵犯轉移; 雷帕黴素標靶蛋白複合體之訊息傳導與調控機制

My main research interest is in the molecular mechanisms of cancer progression, especially in the intricate molecular network that mediates and regulates directional cell migration, i.e. a cell behavior pivotal in cancer invasion/metastasis. Metastasis is a major cause of death in cancer patients. In the process of metastasis, cancer cells undergo multiple steps, including invasion into surrounding tissues, intravasation into blood or lymphatic vessels, and extravasation to new site to colonize, and all these major steps involve cancer cell migration in response to signaling cues present in the tumor microenvironment. Therefore, the development of migration-targeting therapeutics is an attractive goal to pursue for battling cancer mortality and morbidity. Towards this end, a better understanding of the molecular network regulating the directional migration of cancer cells is instrumental.

1. Cell migration and cancer invasion/metastasis– We have previously employed a “forward genetics” approach and discovered some novel molecular players involved in regulating cell migration. Currently, we are investigating several novel regulators to elucidate their molecular functions, and also studying their roles in modulating cancer cell migration and invasion. An example is the protein we named Costars. Cells lacking Costars are severely defective in cell motility, showing abnormal actin patterns and dynamics, forming multiple pseudopods when encountering a chemoattractant gradient, and displaying a decreased migration speed. The Costars protein appears highly conserved among diverse species. Our analyses show that the human homolog of Costars is involved in modulating cancer cell migration and has a role in tumorigenesis and cancer progression. We are currently investigating the underlying molecular mechanisms.
2. TORC2 signaling– Target of rapamycin (TOR) is a conserved Ser/Thr kinase which integrates diverse signals to control growth and maintain homeostasis in response to external stimuli or stress. Dysregulation of TOR functions is associated with various human diseases including cancer. TOR forms two distinct multi-protein complexes, TORC1 and TORC2, which are conserved from yeasts to mammals. Each of the TOR complexes regulates specific functions: TORC1 regulates growth/proliferation-related cellular processes while TORC2 is linked to the control of actin organization. As actin regulation is a TORC2-specific function and our understanding of TORC2 signaling is rather limited (compared to what is known about TORC1 pathways), we have been interested in the mechanisms of TORC2-mediated signaling. We are currently studying the molecular mechanisms underlying TORC2 functions in the budding yeast and human cancer cells.

研究著作

Lin CH, Liao CC, Wang SY, Peng CY, Yeh YC, Chen MY*, and Chou TY*: Comparative O-GlcNAc Proteomic Analysis Reveals a Role of O-GlcNAcylated SAM68 in Lung Cancer Aggressiveness. Cancers 2022, 14:243.

Lin YY, Wang YC, Yeh DW, Hung CY, Yeh YC, Ho HL, Mon HC, Chen MY, Wu YC, and Chou TY*: Gene Expression Profile in Primary Tumor Is Associated with Brain-Tropism of Metastasis from Lung Adenocarcinoma. Int J Mol Sci 2021, 22:13374.

Lin CH, Liao CC, Chen MY*, Chou TY*: Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis. Int J Mol Sci 2021, 22:3463.

Hsiao BY, Chen CH, Chi HY, Yen PR, Yu YZ, Lin CH, Pang TL, Lin WC, Li ML, Yeh YC, Chou TY, Chen MY*: Human Costars Family Protein ABRACL Modulates Actin Dynamics and Cell Migration and Associates with Tumorigenic Growth. Int J Mol Sci 2021, 22:2037.

Lin SC, Lin CH, Shih NC, Liu HL, Wang WC, Lin KY, Liu ZY, Tseng YJ, Chang HK, Lin YC, Yeh YC, Minato H, Fujii T, Wu YC, Chen MY*, Chou TY*: Cellular prion protein transcriptionally regulated by NFIL3 enhances lung cancer cell lamellipodium formation and migration through JNK signaling. Oncogene 2020, 39:385-98.

Lin YC, Lin CH, Yeh YC, Ho HL, Wu YC, Chen MY*, Chou TY*: High O-linked N-acetylglucosamine transferase expression predicts poor survival in patients with early stage lung adenocarcinoma. Oncotarget 2018, 9:31032-44.

Lin YH, Zhen YY, Chien KY, Lee IC, Lin WC, Chen MY, Pai LM: LIMCH1 regulates nonmuscle myosin-II activity and suppresses cell migration. Molecular biology of the cell 2017, 28:1054-65.

Chiu CH, Ho HL, Doong H, Yeh YC, Chen MY, Chou TY, Tsai CM: MLH1 V384D polymorphism associates with poor response to EGFR tyrosine kinase inhibitors in patients with EGFR L858R-positive lung adenocarcinoma. Oncotarget 2015, 6:8407-17.

Lin WC, Wang LC, Pang TL, Chen MY*: Actin binding protein G (AbpG) participates in modulating the actin cytoskeleton and cell migration in Dictyostelium discoideum. Molecular biology of the cell 2015, 26:1084-97.

Hsiao BY, Chang TK, Wu IT, Chen MY*: Rad GTPase inhibits the NFkappaB pathway through interacting with RelA/p65 to impede its DNA binding and target gene transactivation. Cellular signalling 2014, 26:1437-44.

Lin YC, Chen YN, Lin KF, Wang FF, Chou TY*, Chen MY*: Association of p21 with NF-YA suppresses the expression of Polo-like kinase 1 and prevents mitotic death in response to DNA damage. Cell death & disease 2014, 5:e987.

Wang JQ, Chen JH, Chen YC, Chen MY, Hsieh CY, Teng SC, Wu KJ: Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through specific domains. PloS one 2013, 8:e65586.

Leu SJJ, Sung JS, Huang ML, Chen MY, Tsai TW: A novel anti-CCN1 monoclonal antibody suppresses Rac-dependent cytoskeletal reorganization and migratory activities in breast cancer cells. Biochemical and biophysical research communications 2013, 434:885-91.

Leu SJJ, Sung JS, Chen MY, Chen CW, Cheng JY, Wang TY, Wang JJ: The matricellular protein CCN1 suppresses lung cancer cell growth by inducing senescence via the p53/p21 pathway. Journal of cellular biochemistry 2013, 114:2082-93.

Liao HC, Chen MY*: Target of rapamycin complex 2 signals to downstream effector yeast protein kinase 2 (Ypk2) through adheres-voraciously-to-target-of-rapamycin-2 protein 1 (Avo1) in Saccharomyces cerevisiae. The Journal of biological chemistry 2012, 287:6089-99.

Pang TL, Chen FC, Weng YL, Liao HC, Yi YH, Ho CL, Lin CH, Chen MY*: Costars, a Dictyostelium protein similar to the C-terminal domain of STARS, regulates the actin cytoskeleton and motility. Journal of cell science 2010, 123:3745-55.

Chou TY, Chen WC, Lee AC, Hung SM, Shih NY, Chen MY*: Clusterin silencing in human lung adenocarcinoma cells induces a mesenchymal-to-epithelial transition through modulating the ERK/Slug pathway. Cellular signalling 2009, 21:704-11.

Chen CY, Yang KY, Chen MY, Chen HY, Lin MT, Lee YC, Perng RP, Hsieh SL, Yang PC, Chou TY: Decoy receptor 3 levels in peripheral blood predict outcomes of acute respiratory distress syndrome. American journal of respiratory and critical care medicine 2009, 180:751-60.

Ho HL, Lee HY, Liao HC, Chen MY*: Involvement of Saccharomyces cerevisiae Avo3p/Tsc11p in maintaining TOR complex 2 integrity and coupling to downstream signaling. Eukaryotic cell 2008, 7:1328-43.

Pang TL, Wu CJ, Chen PA, Weng YL, Chen MY*: Dictyostelium gnt15 encodes a protein with similarity to LARGE and plays an essential role in development. Biochemical and biophysical research communications 2007, 360:83-9.

Ho HL, Shiau YS, Chen MY*: Saccharomyces cerevisiae TSC11/AVO3 participates in regulating cell integrity and functionally interacts with components of the Tor2 complex. Current genetics 2005, 47:273-88.