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WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2.


ABSTRACT: Lymph node (LN) metastasis is one of the key prognostic factors in bladder cancer, but its underlying mechanisms remain unclear. Here, we found that elevated expression of WD repeat domain 4 (WDR4) in bladder cancer correlated with worse prognosis. WDR4 can promote the LN metastasis and proliferation of bladder cancer cells. Mechanistic studies showed that WDR4 can promote the nuclear localization of DEAD-box helicase 20 (DDX20) and act as an adaptor to bind DDX20 and Early growth response 1 (Egr1), thereby inhibiting Egr1-promoted transcriptional expression of arrestin beta 2 (ARRB2) and ultimately contributing to the progression of bladder cancer. Immunohistochemical analysis confirmed that WDR4 expression is also an independent predictor of LN metastasis in bladder cancer. Our results reveal a novel mechanism of LN metastasis and progression in bladder cancer and identify WDR4 as a potential therapeutic target for metastatic bladder cancer.

SUBMITTER: Wang G 

PROVIDER: S-EPMC10545698 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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WDR4 promotes the progression and lymphatic metastasis of bladder cancer via transcriptional down-regulation of ARRB2.

Wang Guoli G   He Xin X   Dai Huiqi H   Lin Lingyi L   Cao Wenmin W   Fu Yao Y   Diao Wenli W   Ding Meng M   Zhang Qing Q   Chen Wei W   Guo Hongqian H  

Oncogenesis 20231002 1


Lymph node (LN) metastasis is one of the key prognostic factors in bladder cancer, but its underlying mechanisms remain unclear. Here, we found that elevated expression of WD repeat domain 4 (WDR4) in bladder cancer correlated with worse prognosis. WDR4 can promote the LN metastasis and proliferation of bladder cancer cells. Mechanistic studies showed that WDR4 can promote the nuclear localization of DEAD-box helicase 20 (DDX20) and act as an adaptor to bind DDX20 and Early growth response 1 (Eg  ...[more]

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