Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Biology

Collaborative Specialization

Developmental Biology

Supervisor

Dagnino, Lina

2nd Supervisor

Damjanovski, Sashko

Co-Supervisor

Abstract

Kindlin-1 is a scaffold protein linking the cytoskeleton to the extracellular matrix. Loss of function mutations in the FERMT1 gene (encoding Kindlin-1) cause gastrointestinal and skin defects associated with increased susceptibility to aggressive epidermal squamous cell carcinoma (SCC). This study investigated the consequences of targeted FERMT1 inactivation in the SCC-13 cell line of epidermal SCC. My studies demonstrate Kindlin-1 is not essential for SCC-13 proliferation or clonogenic potential in culture. Kindlin-1 was required for cell spreading on collagen I, but not on laminin-332, and its absence enhanced SCC-13 directional migration. Finally, I identified several proteins involved in tumor formation and progression as novel potential targets of Kindlin-1 modulation in SCC-13 cells. To my knowledge, this is the first study evaluating Kindlin-1 function in human epidermal SCC cells, providing novel insights into the role of Kindlin-1 in epidermal carcinomas, which may aid in the development of therapies for cutaneous SCC.

Summary for Lay Audience

Kindlin-1 is a necessary component of cells in the outermost layer of the skin, called the epidermis. Lack of Kindlin-1 in the body causes Kindler syndrome; a hereditary disease that gives rise to skin abnormalities. Humans with Kindler syndrome often develop cancer in the epidermis that is likely to spread throughout the body without medical intervention; known as squamous cell carcinoma (SCC). I studied the role of Kindlin-1 in cells called SCC-13, which are epidermal SCC cells. I compared SCC-13 cells that have Kindlin-1 with SCC-13 cells that were modified so that Kindlin-1 is no longer present. I found Kindlin-1 is not needed for the proliferation of SCC-13 cells. Cells without Kindlin-1 did not spread well, but they showed increased forward movement. Finally, I identified many proteins important for cancer formation and progression that are regulated by Kindlin-1. This study is the first of its kind to evaluate Kindlin-1 function in human epidermal SCC, and increases our understanding of Kindlin-1 function, important for the development of SCC treatments.

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Available for download on Wednesday, December 20, 2023

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