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Zinc finger protein 367 promotes metastasis by inhibiting the Hippo pathway in breast cancer


Circulating tumor cells (CTC) disseminating is an important cause of distant metastasis. However, the mechanism involved in increasing the numbers of CTCs in breast cancer is unclear. Herein, Zinc finger protein 367 (ZNF367) was identified as a potential prometastatic gene in an integrative breast cancer datasets. ZNF367 was upregulated in breast cancer tissues and cell lines, and significantly correlated with poorer metastasis-free and overall survivals in patients. ZNF367 promoted tumor metastasis accompanied with increase of CTC numbers. Mechanistically, ZNF367 interacted with chromatin remodeling protein BRG1 and transcriptionally activated CIT and TP53BP2, leading to the inhibition of the Hippo pathway and activation of YAP1, which gave rise to the resistance of anoikis and increased CTCs in the blood circulation. More importantly, administration of a YAP1 inhibitor Verteporfin resensitized ZNF367-overexpressing breast cancer cells to anoikis and abrogated metastasis. Our findings addressed the importance of ZNF367 in breast cancer as a prognostic biomarker and offered a potential therapeutic strategy for the treatment of a subset of metastatic breast cancer with ZNF367 overexpression.

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Fig. 1: High expression of ZNF367 correlates with breast cancer metastasis and poor prognosis.
Fig. 2: ZNF367 promotes breast cancer metastasis by increasing the presence of CTCs.
Fig. 3: ZNF367 inhibits anoikis in breast cancer.
Fig. 4: ZNF367 activates YAP1 signaling.
Fig. 5: ZNF367 directly activates two negative regulators of the Hippo signaling pathway.
Fig. 6: Pharmacological targeting of YAP1 inhibits ZNF367-driven breast cancer metastasis.
Fig. 7: Clinical relevance of ZNF367 with YAP1 and CTCs in breast cancer patients.


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This work was supported by National Natural Science Foundation of China (No. 81772800); Fundamental Research Funds for the Central Universities (No. 2017KFYXJJ258).

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PL and XL designed the project. XW, XZ, and LY carried out most of the experimental work. XW and XZ conducted the bioinformatic analysis, immunohistochemistry staining, and in vivo studies. CZ, LY, YL, and XS conducted western blot analysis, plasmid constructs, and immunoprecipitation. LY, YO, and XC conducted cell culture and PCR analysis. DR conducted language editing. PL and XL wrote the manuscript. LS, PL, and XL supervised the project.

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Correspondence to Pian Liu or Xi Lin.

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Wu, X., Zhang, X., Yu, L. et al. Zinc finger protein 367 promotes metastasis by inhibiting the Hippo pathway in breast cancer. Oncogene 39, 2568–2582 (2020).

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