Overexpression of CDC42SE1 in A431 cells reduced cell proliferation by inhibiting the Akt pathway
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 C...
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sg-ntu-dr.10356-1047852023-02-28T17:05:17Z Overexpression of CDC42SE1 in A431 cells reduced cell proliferation by inhibiting the Akt pathway Kalailingam, Pazhanichamy Tan, Hui Bing Pan, Jiun Yit Tan, Suat Hoon Thanabalu, Thirumaran School of Biological Sciences CDC42 Skin Cancer DRNTU::Science::Biological sciences 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. MOE (Min. of Education, S’pore) Published version 2019-06-11T01:19:54Z 2019-12-06T21:39:40Z 2019-06-11T01:19:54Z 2019-12-06T21:39:40Z 2019 Journal Article Kalailingam, P., Tan, H. B., Pan, J. Y., Tan, S. H., & Thanabalu, T. (2019). Overexpression of CDC42SE1 in A431 cells reduced cell proliferation by inhibiting the Akt pathway. Cells, 8(2), 117-. doi:10.3390/cells8020117 2073-4409 https://hdl.handle.net/10356/104785 http://hdl.handle.net/10220/48621 10.3390/cells8020117 en Cells © 2019 The Author(s). Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 21 p. application/pdf |
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CDC42 Skin Cancer DRNTU::Science::Biological sciences Kalailingam, Pazhanichamy Tan, Hui Bing Pan, Jiun Yit Tan, Suat Hoon Thanabalu, Thirumaran Overexpression of CDC42SE1 in A431 cells reduced cell proliferation by inhibiting the Akt pathway |
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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. |
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School of Biological Sciences |
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School of Biological Sciences Kalailingam, Pazhanichamy Tan, Hui Bing Pan, Jiun Yit Tan, Suat Hoon Thanabalu, Thirumaran |
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Article |
author |
Kalailingam, Pazhanichamy Tan, Hui Bing Pan, Jiun Yit Tan, Suat Hoon Thanabalu, Thirumaran |
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Kalailingam, Pazhanichamy |
title |
Overexpression of CDC42SE1 in A431 cells reduced cell proliferation by inhibiting the Akt pathway |
title_short |
Overexpression of CDC42SE1 in A431 cells reduced cell proliferation by inhibiting the Akt pathway |
title_full |
Overexpression of CDC42SE1 in A431 cells reduced cell proliferation by inhibiting the Akt pathway |
title_fullStr |
Overexpression of CDC42SE1 in A431 cells reduced cell proliferation by inhibiting the Akt pathway |
title_full_unstemmed |
Overexpression of CDC42SE1 in A431 cells reduced cell proliferation by inhibiting the Akt pathway |
title_sort |
overexpression of cdc42se1 in a431 cells reduced cell proliferation by inhibiting the akt pathway |
publishDate |
2019 |
url |
https://hdl.handle.net/10356/104785 http://hdl.handle.net/10220/48621 |
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1759856910880735232 |