Interactions Between Tpm3.1 and YAP In Melanoma Cell Proliferation.

Gathier, Y. (Yvonne) (2015) Interactions Between Tpm3.1 and YAP In Melanoma Cell Proliferation. thesis, Medicine.

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Abstract

Australia has the highest melanoma incidence rates worldwide, with 11,570 new cases and 1,544 deaths from melanoma in 2011. In 2020 an estimated 17,570 Australians will be diagnosed with melanoma of the skin. This poses an extreme burden on the health care system. To aid in the development of new therapies, it is important to better understand the molecular mechanisms underlying skin carcinogenesis. The Hippo-/YAP pathway and the tropomyosin Tpm3.1 both play pivotal roles in the regulation of cell proliferation and tissue homeostasis. Recent evidence suggests that YAP activity is controlled by external mechanical acting on the actin architecture and regulating cellular tension, which in turn is regulated by Tpm3.1. This study aimed to investigate if Tpm3.1 controls the activity of YAP in melanoma cell proliferation. We found that YAP and Tpm3.1 are co-expressed in MelRM and MelRMu melanoma cells. PLA-assays showed direct protein-protein interactions between YAP and Tpm3.1 in both cell types. Knock-down of Tpm3.1 using siRNA appeared to affect YAP localisation and expression in MelRMu cells. Interestingly, we also detected higher expression levels of both Tpm3.1 and YAP in MelRM cells with wildtype BRaf compared to MelRMu cells with the BRaf activating mutation V600E. This study provides evidence that Tpm3.1 regulates melanoma cell proliferation through controlling YAP localization. In addition, our data reveals a possible regulatory mechanism between BRaf and YAP and Tpm3.1 expression in proliferating melanoma cells.

Item Type:	Thesis (Thesis)
Supervisor name:	Terra, Dr. J.T.
Supervisor name:	Beverdam, Dr. A. and UNSW, Sydney
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:06
Last Modified:	25 Jun 2020 11:06
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2568

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