RUVBL1-ITFG1 interaction is required for collective invasion in breast cancer.
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.



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.



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.



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



Targeting collective invasion promoted by RUVBL1-ITFG1 complex provides a novel therapeutic strategy to improve the prognosis of invasive breast cancer.
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Wenjun
W
Fan
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China; Department of Hematology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Jiajun
J
Xie
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Jianglong
J
Xia
Yale Stem Cell Center, Department of Genetics, Yale University, New Haven, CT, USA.
Yan
Y
Zhang
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Mengying
M
Yang
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Hefei
H
Wang
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Yujia
Y
Pan
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Mengjuan
M
Zhang
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Baochun
B
Han
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Baitong
B
Wu
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Zhijie
Z
Hou
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Dapeng
D
Liang
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Chunli
C
Wang
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
Jie
J
Xu
Liaoning Key Laboratory of Petrochemical Engineering, Liaoning Shihua University, Fushun, China.
Lijuan
L
Song
Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. Electronic address: liuq9@mail.sysu.edu.cn.
Quentin
Q
Liu
D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D045744:Cell Line, Tumor; D004265:DNA Helicases / Q000032:analysis / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011485:Protein Binding
D002352:Carrier Proteins; C000624320:ITFG1 protein, human; D008565:Membrane Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C486549:RUVBL1 protein, human
Breast cancer; Collective invasion; ITFG1; Microfluidic; RUVBL1