Thesis Format
Monograph
Degree
Master of Science
Program
Physiology and Pharmacology
Collaborative Specialization
Developmental Biology
Supervisor
Dagnino, Lina
Abstract
Kindlin-2 is a scaffold protein with an important role in activating integrins, which link the cytoskeleton to the extracellular matrix. In epidermal keratinocytes, loss of Kindlin-2 alters adhesion, spreading, proliferation, migration, and formation of focal adhesions and cell-cell junctions, suggesting its importance in the growth and motility of epidermal cells. This study investigated the consequences of targeted FERMT2-silencing in an actinic keratosis lesion and cutaneous squamous carcinoma cell lines. My data demonstrate that Kindlin-2 deficiency decreases the rate of directional migration of all cell lines. However, reduced proliferation and spreading and alterations in focal adhesion and F-actin and microtubule cytoskeletal organization were only observed in the actinic keratosis and metastatic cutaneous squamous carcinoma cell line. To the best of my knowledge, these are novel results evaluating the role of Kindlin-2 in human epidermal carcinomas, which may aid in the development of therapies for cutaneous squamous cell carcinoma (cSCC).
Summary for Lay Audience
The skin is the largest organ in the body. The epidermis, which is the outermost layer of the skin, is a protective barrier between the body and bacteria, viruses, and damaging UV light from the sun. Cumulative exposure of the epidermis to UV radiation can lead to the formation of cancers called cutaneous squamous cell carcinomas (cSCC). My study aims at understanding the role that a protein known as Kindlin-2 plays in regulating cSCC characteristics. To this end, I created models of cSCC cells that have lower Kindlin-2 abundance, and compared them with similar cSCC cells that have normal levels of Kindlin-2. I determined that Kindlin-2 contributes to the forward movements of these cells. Kindlin-2 is also needed for normal growth of some, but not all, cSCC cells. My study is the first to explore the role of Kindlin-2 in these defining characteristics of abnormal epidermal cells. My results may potentially contribute to building new treatments for skin carcinomas.
Recommended Citation
Dutta, Anamika, "Kindlin-2 Modulates Proliferation and Migration of Actinic Keratosis Lesions and Metastatic cSCC Cells" (2025). Electronic Thesis and Dissertation Repository. 10801.
https://ir.lib.uwo.ca/etd/10801