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計畫

負責人

計畫重點

子計畫一

張心儀

Proteomic analysis of resistant CRC cellsInvestigation the composition of plasma membrane proteome, phosphoproteome, and kinome to define a precise drug responsiveness niche of resistant cells.

子計畫二

黃翠琴

Metabolism reprogramming in the resistant CRC cellsInvestigation the underling molecular mechanism leading toward mitochondria fission and rewired metabolic pathway causing oxaliplatin resistance.

子計畫三

李育誠

Tumor microenvironment and chemoresistanceStudy the contributions of stromal cells promote colorectal cancer progression and chemoresistance through reciprocal communication with the refractory cancer cells.

計畫主持人

李崑豪

Metastatic potential and drug resistanceInvestigation strong mediators of metastatic-TM4SF1/DDR1 in the resistant CRC cells.

子計畫五

鄭嘉雄

DNA repair in resistant CRC cells using zebrafish tumor xenograft modelInvestigation investigate the function of UBE2S on DNA repair in oxaliplatin-resistance colon cancer and evaluate the inhibition effects of SMD-B1 in drug resistant colon cancer cells and zebrafish tumor xenograft model.

 

研究主題:Investigation the Mechanism of Drug Resistance in Colorectal cancer (CRC) and Develop Novel Treatment Strategies

研究摘要

  The treatment strategies of metastatic colorectal cancer (mCRC) largely correlate with drug resistance mechanisms, Subproject 1 and 2 have established 5-FU- and oxaliplatin-resistant CRC cell lines. The roles of some mediators (including metabolism, EMT, tumor microenvironment, and DNA repair) in resistant CRC cells will be further investigated in the all Subprojects. In addition, Subproject 1 investigated the composition of plasma membrane proteome, phosphoproteome, and kinome of resistant CRC cells, which will provide the proof of concept of molecules involved in tumor microenvironment (Subproject 3) and metastasis (Subproject 4). In Subproject 3, how does surrounding stromal cells of CRC respond to resistant cells-derived cytokines, leading to other cytokines release will be investigated. The very recent study indicated metastasis can occur early in human colorectal cancer before diagnosis and highlights the critical need to identify specific molecules in metastasis. Thus, in Subproject 4, the functional role and molecular mechanism of strong mediators of metastatic-TM4SF1/DDR1 in metastasis and resistant CRC cells will be investigated. DNA repair potential has to be taken into account attempting to chemotherapy and a high activity of DNA repair genes was hypothesized as a predisposition to metastasis. Therefore, Subproject 5 investigated the function of ubiquitin-conjugating enzyme E2 S (UBE2S) on DNA repair in resistance CRC cells and evaluate the inhibition effects of SMD-B1 in drug resistant CRC cells and zebrafish tumor xenograft model. Zebrafish have been shown as a metastasis model of cancer cells and the visible zebrafish embryo has the advantage of being able to analyze the metastasis of human tumor cells with fluorescent labeling. Therefore, zebrafish tumor xenograft model of Subproject 5 will also provide the platform to study the functional roles of potential mediators from all the subprojects in vivo.

                                

                                  

研究成果