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Cells 2019, 8(2), 117;

Overexpression of CDC42SE1 in A431 Cells Reduced Cell Proliferation by Inhibiting the Akt Pathway

School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore
National Skin Centre, Singapore 308205, Singapore
Author to whom correspondence should be addressed.
Present address: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 MD Drive, Singapore 117596, Singapore.
Present address: National University Health System, 1E Kent Ridge Road, Singapore 119228, Singapore.
Received: 19 December 2018 / Revised: 25 January 2019 / Accepted: 30 January 2019 / Published: 2 February 2019
(This article belongs to the Special Issue Rho GTPases in Health and Disease)
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Cell division cycle 42 (CDC42), a small Rho GTPase, plays a critical role in many cellular processes, including cell proliferation and survival. CDC42 interacts with the CRIB (Cdc42- and Rac-interactive binding) domain of CDC42SE1, a small effector protein of 9 kDa. We found that the expression of CDC42SE1 was reduced in human skin cancer samples relative to matched perilesional control. Exogenous expression of CDC42SE1 but not CDC42SE1H38A (mutation within CRIB domain) in A431 cells (A431SE1, A431SE1-H38A) reduced cell proliferation. Antibody microarray analysis of A431Ctrl and A431SE1 lysate suggested that reduced A431SE1 cells proliferation was due to inhibition of Akt pathway, which was confirmed by the reduced P-Akt and P-mTOR levels in A431SE1 cells compared to A431Ctrl cells. This suggests that CDC42SE1 modulates the CDC42-mediated Akt pathway by competing with other effector proteins to bind CDC42. A431SE1 cells formed smaller colonies in soft agar compared to A431Ctrl and A431SE1-H38A cells. These findings correlate with nude mice xenograft assays, where A431SE1 cells formed tumors with significantly-reduced volume compared to the tumors formed by A431Ctrl cells. Our results suggest that CDC42SE1 is downregulated in skin cancer to promote tumorigenesis, and thus CDC42SE1 might be an important marker of skin cancer progression. View Full-Text
Keywords: CDC42; skin cancer; Akt pathway; actin cytoskeleton CDC42; skin cancer; Akt pathway; actin cytoskeleton

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Kalailingam, P.; Tan, H.B.; Pan, J.Y.; Tan, S.H.; Thanabalu, T. Overexpression of CDC42SE1 in A431 Cells Reduced Cell Proliferation by Inhibiting the Akt Pathway. Cells 2019, 8, 117.

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