To investigate the role of STK4 defect to promote premature aging and tumor progression in C elegans and human cancer models

  • 許 太乙

Student thesis: Doctoral Thesis

Abstract

STK4 is a serine/threonine kinase protein encoded for 487 amino acids which plays an important role in Hippo pathway involved in development progression Disease associated with STK4 down-regulation induces tumor recurrent and hepatocellular carcinoma formation However the regulation mechanism of protein expression and function are still not clear To address the STK4 protein function in the creatures that model organism C elegans were used to answer this question The intestinal tract distance of cst-1 knock-out has wider than control group and premature aging has been shown ?-catenin homologous bar-1 is also involved in intestinal tract development regulation mechanism The premature aging and intestine abnormality can be restored under bar-1 down-regulated with cst-1 over-expressed STK4 protein expression level regulation mechanism is still unknown One possibility is post-transcriptional regulation through miRNA targeting mRNA 3’UTR degradation The function assay and clinical samples showed that miR-18a indeed is an oncomiR to suppress STK4 induced apoptosis cascade through AKT phosphorylation regulation Above the data from C elegans beta-catenin can be the candidate target interacted with STK4 in the same axis to regulate digestive tract development IHC staining of different kinds of tumor parts showed that STK4 are highly expressed in prostate liver and colon compared with normal specimens All of our study indicated that STK4 is a tumor suppressor interacted with beta-catenin in prostate and colon cancers The protein synthesis is through miRNA mediated degradation The study demonstrated that STK4 can be the therapeutic target for prostate and colon cancer
Date of Award2016 May 30
Original languageEnglish
SupervisorPei-Jung Lu (Supervisor)

Cite this

To investigate the role of STK4 defect to promote premature aging and tumor progression in C elegans and human cancer models
太乙, 許. (Author). 2016 May 30

Student thesis: Doctoral Thesis