Chemistry and Chemical Biology ETDs

Publication Date

Fall 9-21-2021

Abstract

Cancer is one of the biggest threatens to human health. Colon cancer is one of the leading causes of new incidence and mortality in the whole world. It is important to understand the mechanism of tumorigenesis and development. Based on the mechanisms, we may develop new therapeutics to improve survival rate.

In Chapter 2, we discussed the PINK1 function in suppression colon cancer. We found that PINK1 can activate its substrate P53, which activates its downstream targets during mitophay. At the same time, PINK1 is also involved in metabolism, we showed that PINK1 can reduce Acetyl-CoA by inhibiting PDHE1ɑ. Cells treated with acetate can rescue PINK1 suppression role in colon cancer.

In Chapter 3 we investigated PINK1’s role in inflammation. We found that some cytokines involved in immune response significantly changed. In this on-going project , the mechanism is still elusive, and we need figure out the reasons and provide a potential method for colon cancer treatment.

In Chapter 4, we studied STEAP4, which promotes tumor development. We found that STEA4 deficiency has a protection role in colon cancer development, and in vitro study showed that STEAP4 promoted tumor cell growth by increasing ROS level, which can also trigger cell death. We used two drugs that can induce ROS to treat the cells, and it showed that these two drugs can induce apoptosis in STEAP4 overexpression cell line. These findings may provide a potential treatment for colon cancer.

Project Sponsors

Prof. XIANG XUE

Language

English

Keywords

colon cnacer, PINK1, acetyl-CoA, inflammation, STEAP4, ROS

Document Type

Dissertation

Degree Name

Chemistry

Level of Degree

Doctoral

Department Name

Department of Chemistry and Chemical Biology

First Committee Member (Chair)

Prof. Jeremy Edwards

Second Committee Member

Prof. Xiang Xue

Third Committee Member

Prof. Changjian Feng

Fourth Committee Member

Prof. Mark Walker

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