Introduction to Project on the Role of the C-terminal domain of Cxcr3 in Cxcl10-induced Breast Cancer Cell Migration
Introduction
Hello new readers! Welcome to my senior project updates page. My project is focused on triple-negative breast cancer (TNBC) metastasis. My name is Christopher Yoo, and I had the opportunity to work for 8 weeks as a summer intern in a breast cancer research lab at the Translational Genomics Research Institute. My summer research project was a part of the larger investigation of the role of chemokine signaling in breast cancer. This senior project is a continuation of the work I did at the summer internship on the chemokine receptor Cxcr3.
Project Description
Triple-negative breast cancer (TNBC) lacks common breast cancer receptors (estrogen, progesterone, and HER2) that can be targeted by therapeutics. With current treatments, over 40% of women with TNBC see recurrence within 5 years, and less than 12% with distant metastatic TNBC survive past 5 years.
Tumor suppressor genes encode for proteins that inhibit tumor formation and development. Up to 34% of all breast cancer tumors are deficient in the tumor suppressor Inhibitor of Growth 4 (ING4) and correlated with poor patient survival. Chemokines are signaling proteins that induce directional movement mostly in immune cells. Higher concentration of Cxcl10 in ING4-deficient TNBC incites cell migration and tumor metastasis in experimental systems. Clinically relevant, patients with Cxcl10-high/ING4-low expressing breast tumors have significantly reduced disease-free survival.
Cxcl10 binds the seven transmembrane domain G protein-coupled receptor Cxcr3 to signal cell migration. The carboxyl-terminus is the end of an amino acid chain. The carboxyl-terminal intracellular domain of Cxcr3 has been shown to promote chemotactic migration in lymphocytes (immune system response cells). However, the specific effects of Cxcr3’s carboxyl-terminus in TNBC is unknown.
Project Goal
The main question I plan to research is “What is the main function of the c-terminal end of Cxcr3 in breast cancer cell migration?” My hypothesis is that this cytoplasmic portion of Cxcr3 is necessary for Cxcl10-induced cell migration. The goal of my project is to investigate a mutant gene encoding for the shortened chemokine receptor Cxcr3. Another question that this project may address is if treatment options targeting this c-terminal end of Cxcr3 are possible. My current project is planned to take a cell line expressing the mutant gene from my previous internship and compare it to normal breast cancer cells for cell migration.
Please check the attached project proposal draft for a more in-depth description of the project and my previous internship work.