| Summary: | 碩士 === 輔仁大學 === 生命科學系碩士班 === 97 === By integrating three gene expression profile datasets, including pairwise female lung adenocarcinoma, secondary metastatic tumors vs. benign tumors, and lung adenocarinoma metastasis to brain, we have identified some novel metastasis-associated genes in lung adenocarcinoma. In this thesis, I focus on one poorly characterized gene, KIAA0101, and demonstrated the higher level of KIAA0101 expression is found in many lung cancer cell lines as compared to normal lung fibroblast. Knock-down the expression of KIAA0101 significantly decreased the migration and invasion ability of H1299 cells, while over-expression of KIAA0101 increased these events in CL1-0 cells, indicating KIAA0101 may play a role in promoting cell migration and invasion. Similar results are evidenced in stable KIAA0101 over-expression cells, which display higher growth rate and migration rate than vehicle cells, and promote tumor formation in nude mice in vivo. Since c-terminal truncate form of KIAA0101 (1~60 a.a.) almost lost it’s ability to promote cell migration, we speculate that PCNA binding or the WW4 motif, which is located between 62 ~73 a.a., may be crucial for KIAA0101 elicited cell migration. In addition, the presence of MMP inhibitor can decrease KIAA0101 induced cell migration and invasion and the decrease of E-cadherin expression was found in stable KIAA0101 over-expression cells, indicating KIAA0101 may concurrently regulate EMT event and MMP activity to affect cell migration and invasion. In accordance with the situation on lung cancer cell, the expression level of KIAA0101 is high in HCC tumor tissue and correlates with the migration abilities of HCC cell lines. Overall, this thesis demonstrated KIAA0101 could promote cell migration, invasion and tumorgenesis, which may be a promising target for cancer therapeutics or prognosis.
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