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    VASP activation via the Gα13/RhoA/PKA pathway mediates cucurbitacin-B-induced actin aggregation and cofilin-actin rod formation

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    Author
    Zhang, Yan-Ting; Xu, Li-Hui; Lu, Qun; Liu, Kun-Peng; Liu, Pei-Yan; Ji, Fang; Liu, Xiao-Ming; Ouyang, Dong-Yun; He, Xian-Hui
    Abstract
    Cucurbitacin B (CuB), a potent antineoplastic agent of cucurbitacin triterpenoids, induces rapid disruption of actin cytoskeleton and aberrant cell cycle inhibiting carcinogenesis. However, the underlying molecular mechanism of such anticancer effects remains incompletely understood. In this study, we showed that CuB treatment rapidly induced vasodilator-stimulated phosphoprotein (VASP) phosphorylation (i.e. activation) at the Ser157 residue and generated VASP clumps which were co-localized with amorphous actin aggregates prior to the formation of highly-ordered cofilin-actin rods in melanoma cells. Knockdown of VASP or inhibition of VASP activation using PKA-specific inhibitor H89 suppressed CuB-induced VASP activation, actin aggregation and cofilin-actin rod formation. The VASP activation was mediated by cAMP-independent PKA activation as CuB decreased the levels of cAMP while MDL12330A, an inhibitor of adenylyl cyclase, had weak effect on VASP activation. Knockdown of either Gα13 or RhoA not only suppressed VASP activation, but also ameliorated CuB-induced actin aggregation and abrogated cofilin-actin rod formation. Collectively, our studies highlighted that the CuB-induced actin aggregation and cofilin-actin rod formation was mediated via the Gα13/RhoA/PKA/VASP pathway.
    URI
    http://hdl.handle.net/10342/8051
    Date
    2014-04-01
    Citation:
    APA:
    Zhang, Yan-Ting, & Xu, Li-Hui, & Lu, Qun, & Liu, Kun-Peng, & Liu, Pei-Yan, & Ji, Fang, & Liu, Xiao-Ming, & Ouyang, Dong-Yun, & He, Xian-Hui. (April 2014). VASP activation via the Gα13/RhoA/PKA pathway mediates cucurbitacin-B-induced actin aggregation and cofilin-actin rod formation. , (), - . Retrieved from http://hdl.handle.net/10342/8051

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    MLA:
    Zhang, Yan-Ting, and Xu, Li-Hui, and Lu, Qun, and Liu, Kun-Peng, and Liu, Pei-Yan, and Ji, Fang, and Liu, Xiao-Ming, and Ouyang, Dong-Yun, and He, Xian-Hui. "VASP activation via the Gα13/RhoA/PKA pathway mediates cucurbitacin-B-induced actin aggregation and cofilin-actin rod formation". . . (), April 2014. September 30, 2023. http://hdl.handle.net/10342/8051.
    Chicago:
    Zhang, Yan-Ting and Xu, Li-Hui and Lu, Qun and Liu, Kun-Peng and Liu, Pei-Yan and Ji, Fang and Liu, Xiao-Ming and Ouyang, Dong-Yun and He, Xian-Hui, "VASP activation via the Gα13/RhoA/PKA pathway mediates cucurbitacin-B-induced actin aggregation and cofilin-actin rod formation," , no. (April 2014), http://hdl.handle.net/10342/8051 (accessed September 30, 2023).
    AMA:
    Zhang, Yan-Ting, Xu, Li-Hui, Lu, Qun, Liu, Kun-Peng, Liu, Pei-Yan, Ji, Fang, Liu, Xiao-Ming, Ouyang, Dong-Yun, He, Xian-Hui. VASP activation via the Gα13/RhoA/PKA pathway mediates cucurbitacin-B-induced actin aggregation and cofilin-actin rod formation. . April 2014; (): . http://hdl.handle.net/10342/8051. Accessed September 30, 2023.
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