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[Biochimica et Biophysica Acta (BBA) - General Subjects] RUVBL1-ITFG1 interaction is required for co


Abstract:

Background

The mechanisms of breast cancer collective invasion are poorly understood limiting the metastasis therapy. The ATPase RUVBL1 is frequently overexpressed in various cancers and plays a crucial role in oncogenic process. We further investigated the role of RUVBL1 in promoting collective invasion and uncovered that targeting RUVBL1 could inhibit metastatic progression.

Methods

The expression levels of RUVBL1 and ITFG1 were examined by Western blot and qRT-PCR. Co-localization and interaction of RUVBL1 and ITFG1 were determined by immunofluorescence and co-immunoprecipitation. The invasive ability was examined by transwell assay and microfluidic assay. The metastatic and tumorigenic abilities of breast cancer cells were revealed in BALB/c nude mice by xenograft and tail vein injection.

Results

ATPase RUVBL1 is highly expressed in breast cancer and predicts the poor prognosis. Elevated expression of RUVBL1 is found in high metastatic breast cancer cells. Silencing RUVBL1 suppresses cancer cell expansion and invasion in vitro and in vivo. RUVBL1 interacts with a conserved transmembrane protein ITFG1 in cytoplasm and plasma membrane to promote the collective invasion. Using a microfluidic model, we demonstrated that silencing RUVBL1 or ITFG1 individually compromises collective invasion of breast cancer cells.

Conclusion

RUVBL1 is a vital regulator for collective invasion. The interactions between RUVBL1 and ITFG1 are required for breast cancer cell collective invasion and progression.

General Significance

Targeting collective invasion promoted by RUVBL1-ITFG1 complex provides a novel therapeutic strategy to improve the prognosis of invasive breast cancer.

Wenjun Fan a, Jiajun Xie b, c, Jianglong Xia a, Yan Zhang d, Mengying Yang a, Hefei Wang a, Yujia Pan a, Mengjuan Zhang a, Baochun Han a, Baitong Wu a, Zhijie Hou a, Dapeng Liang a, Chunli Wang a, Jie Xu a, Lijuan Song e, Quentin Liu a, b, a Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China b State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China c Department of Hematology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China d Yale Stem Cell Center, Department of Genetics, Yale University, New Haven, CT, USA e Liaoning Key Laboratory of Petrochemical Engineering, Liaoning Shihua University, Fushun, China Received 30 December 2016, Revised 5 March 2017, Accepted 18 March 2017, Available online 21 March 2017 http://dx.doi.org/10.1016/j.bbagen.2017.03.016

Link: http://www.sciencedirect.com/science/article/pii/S0304416517300995

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