Proteomics

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Amiloride reduces FN3K expression to restore sunitinib sensitivity in renal cell carcinoma


ABSTRACT: The kidney is a vital organ responsible for water and sodium metabolism, while the primary function of amiloride is to promote the excretion of water and sodium. We investigated amiloride enhanced the sunitinib sensitivity in RCC. We found both sunitinib and amiloride displayed cytotoxicity and exerted the synergy effect in RCC cells in vivo and in vitro arrays. Protein expression profiles were screened via MS/TMT, revealing that FN3K was upregulated in sunitinib group, and rescued in amiloride and the combination administration. Exogenous FN3K could promote proliferation, invasion and metastasis and decrease the sensitivity of Caki-1 cells to sunitinib, also, exogenous FN3K up-regulated VEGFR2 expression and activated AKT/mTOR signal pathway. More FN3K and VEGFR2 accumulated in R-Caki-1 cells and rescued by amiloride treatment. Co-IP and IF confirmed the interaction between FN3K and VEGFR2. In conclusion, FN3K depletion mediated VEGFR2 disruption promotes amiloride synergized the anti-RCC activity of sunitinib.

ORGANISM(S): Homo Sapiens

SUBMITTER: Yongyang Wu  

PROVIDER: PXD052100 | iProX | Tue May 07 00:00:00 BST 2024

REPOSITORIES: iProX

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Publications

Amiloride reduces fructosamine-3-kinase expression to restore sunitinib sensitivity in renal cell carcinoma.

Bai Yuanyuan Y   You Yiqing Y   Chen Daoxun D   Chen Yongmei Y   Yin Zhenjie Z   Liao Shangfan S   You Bingyong B   Lu Dongming D   Sun Yingming Y   Wu Lixian L   Wu Yongyang Y  

iScience 20240516 6


The kidney is a vital organ responsible for water and sodium metabolism, while the primary function of amiloride is to promote the excretion of water and sodium. We investigated amiloride enhanced the sunitinib sensitivity in RCC. We found both sunitinib and amiloride displayed cytotoxicity and exerted the synergy effect in RCC cells <i>in vivo</i> and <i>in vitro</i> arrays. Protein expression profiles were screened via MS/TMT, revealing that FN3K was upregulated in the sunitinib group, and res  ...[more]

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