RASAL2 inhibits tumor angiogenesis via p-AKT/ETS1 signaling in bladder cancer

Ke Hui; Shiqi Wu; Yangyang Yue; Yanan Gu; Bing Guan; Xinyang Wang; Jer Tsong Hsieh; Luke S. Chang; Dalin He; Kaijie Wu

doi:10.1016/j.cellsig.2018.04.006

RASAL2 inhibits tumor angiogenesis via p-AKT/ETS1 signaling in bladder cancer

Ke Hui, Shiqi Wu, Yangyang Yue, Yanan Gu, Bing Guan, Xinyang Wang, Jer Tsong Hsieh, Luke S. Chang, Dalin He, Kaijie Wu

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Muscle-invasive or metastatic bladder cancer (BCa) is a life-threatening disease for patients, and tumor angiogenesis is believed to play a critical role in the progression of BCa. However, its underlying mechanism of tumor angiogenesis is still poorly understood. In this study, we discovered that RASAL2, a RAS GTPase activating protein, could inhibit BCa angiogenesis based on our shRNA/siRNA knockdown or ectopic cDNA expression experiments. Mechanistically, RASAL2 downregulation could enhance the phosphorylation of AKT and then subsequently upregulate the expression of ETS1 and VEGFA. Furthermore, there was a negative correlation between RASAL2 and VEGFA or CD31 expression in subcutaneous xenograft and human BCa specimens. Taken together, we provide a new insight into the molecular mechanism of BCa progression, in which RASAL2 can be a new therapeutic target.

Original language	English (US)
Pages (from-to)	38-44
Number of pages	7
Journal	Cellular Signalling
Volume	48
DOIs	https://doi.org/10.1016/j.cellsig.2018.04.006
State	Published - Aug 2018

Keywords

AKT/ETS1 signaling
Angiogenesis
Bladder cancer
RASAL2
VEGFA

ASJC Scopus subject areas

Cell Biology

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10.1016/j.cellsig.2018.04.006

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title = "RASAL2 inhibits tumor angiogenesis via p-AKT/ETS1 signaling in bladder cancer",

abstract = "Muscle-invasive or metastatic bladder cancer (BCa) is a life-threatening disease for patients, and tumor angiogenesis is believed to play a critical role in the progression of BCa. However, its underlying mechanism of tumor angiogenesis is still poorly understood. In this study, we discovered that RASAL2, a RAS GTPase activating protein, could inhibit BCa angiogenesis based on our shRNA/siRNA knockdown or ectopic cDNA expression experiments. Mechanistically, RASAL2 downregulation could enhance the phosphorylation of AKT and then subsequently upregulate the expression of ETS1 and VEGFA. Furthermore, there was a negative correlation between RASAL2 and VEGFA or CD31 expression in subcutaneous xenograft and human BCa specimens. Taken together, we provide a new insight into the molecular mechanism of BCa progression, in which RASAL2 can be a new therapeutic target.",

keywords = "AKT/ETS1 signaling, Angiogenesis, Bladder cancer, RASAL2, VEGFA",

author = "Ke Hui and Shiqi Wu and Yangyang Yue and Yanan Gu and Bing Guan and Xinyang Wang and Hsieh, {Jer Tsong} and Chang, {Luke S.} and Dalin He and Kaijie Wu",

note = "Funding Information: This study was supported by the National Natural Science Foundation of China (NSFC 81572516 to KW) and International Science and Technology Cooperation and Exchange Program in Shaanxi Province ( 2016KW-021 to KW). Publisher Copyright: {\textcopyright} 2018",

year = "2018",

month = aug,

doi = "10.1016/j.cellsig.2018.04.006",

language = "English (US)",

volume = "48",

pages = "38--44",

journal = "Cellular Signalling",

issn = "0898-6568",

publisher = "Elsevier Inc.",

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TY - JOUR

T1 - RASAL2 inhibits tumor angiogenesis via p-AKT/ETS1 signaling in bladder cancer

AU - Hui, Ke

AU - Wu, Shiqi

AU - Yue, Yangyang

AU - Gu, Yanan

AU - Guan, Bing

AU - Wang, Xinyang

AU - Hsieh, Jer Tsong

AU - Chang, Luke S.

AU - He, Dalin

AU - Wu, Kaijie

N1 - Funding Information: This study was supported by the National Natural Science Foundation of China (NSFC 81572516 to KW) and International Science and Technology Cooperation and Exchange Program in Shaanxi Province ( 2016KW-021 to KW). Publisher Copyright: © 2018

PY - 2018/8

Y1 - 2018/8

N2 - Muscle-invasive or metastatic bladder cancer (BCa) is a life-threatening disease for patients, and tumor angiogenesis is believed to play a critical role in the progression of BCa. However, its underlying mechanism of tumor angiogenesis is still poorly understood. In this study, we discovered that RASAL2, a RAS GTPase activating protein, could inhibit BCa angiogenesis based on our shRNA/siRNA knockdown or ectopic cDNA expression experiments. Mechanistically, RASAL2 downregulation could enhance the phosphorylation of AKT and then subsequently upregulate the expression of ETS1 and VEGFA. Furthermore, there was a negative correlation between RASAL2 and VEGFA or CD31 expression in subcutaneous xenograft and human BCa specimens. Taken together, we provide a new insight into the molecular mechanism of BCa progression, in which RASAL2 can be a new therapeutic target.

AB - Muscle-invasive or metastatic bladder cancer (BCa) is a life-threatening disease for patients, and tumor angiogenesis is believed to play a critical role in the progression of BCa. However, its underlying mechanism of tumor angiogenesis is still poorly understood. In this study, we discovered that RASAL2, a RAS GTPase activating protein, could inhibit BCa angiogenesis based on our shRNA/siRNA knockdown or ectopic cDNA expression experiments. Mechanistically, RASAL2 downregulation could enhance the phosphorylation of AKT and then subsequently upregulate the expression of ETS1 and VEGFA. Furthermore, there was a negative correlation between RASAL2 and VEGFA or CD31 expression in subcutaneous xenograft and human BCa specimens. Taken together, we provide a new insight into the molecular mechanism of BCa progression, in which RASAL2 can be a new therapeutic target.

KW - AKT/ETS1 signaling

KW - Angiogenesis

KW - Bladder cancer

KW - RASAL2

KW - VEGFA

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DO - 10.1016/j.cellsig.2018.04.006

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AN - SCOPUS:85046171518

SN - 0898-6568

VL - 48

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EP - 44

JO - Cellular Signalling

JF - Cellular Signalling

ER -

RASAL2 inhibits tumor angiogenesis via p-AKT/ETS1 signaling in bladder cancer

Abstract

Keywords

ASJC Scopus subject areas

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