RGD Reference Report - Silencing of atp6v1c1 prevents breast cancer growth and bone metastasis. - Rat Genome Database

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Silencing of atp6v1c1 prevents breast cancer growth and bone metastasis.

Authors: Feng, Shengmei  Zhu, Guochun  McConnell, Matthew  Deng, Lianfu  Zhao, Qiang  Wu, Mengrui  Zhou, Qi  Wang, Jinshen  Qi, Jin  Li, Yi-Ping  Chen, Wei 
Citation: Feng S, etal., Int J Biol Sci. 2013 Sep 5;9(8):853-62. doi: 10.7150/ijbs.6030. eCollection 2013.
RGD ID: 14700647
Pubmed: PMID:24155661   (View Abstract at PubMed)
PMCID: PMC3805834   (View Article at PubMed Central)
DOI: DOI:10.7150/ijbs.6030   (Journal Full-text)

Previous studies have shown that Atp6v1c1, a regulator of the assembly of the V0 and V1 domains of the V-ATPase complex, is up-regulated in metastatic oral tumors. Despite these studies, the function of Atp6v1c1 in tumor growth and metastasis is still unknown. Atp6v1c1's expression in metastatic oral squamous cell carcinoma indicates that Atp6v1c1 has an important function in cancer growth and metastasis. We hypothesized that elevated expression of Atp6v1c1 is essential to cancer growth and metastasis and that Atp6v1c1 promotes cancer growth and metastasis through activation of V-ATPase activity. To test this hypothesis, a Lentivirus-mediated RNAi knockdown approach was used to study the function of Atp6v1c1 in mouse 4T1 mammary tumor cell proliferation and migration in vitro and cancer growth and metastasis in vivo. Our data revealed that silencing of Atp6v1c1 in 4T1 cancer cells inhibited lysosomal acidification and severely impaired 4T1 cell growth, migration, and invasion through Matrigel in vitro. We also show that Atp6v1c1 knockdown with Lenti-c1s3, a lentivirus targeting Atp6v1c1 for shRNA mediated knockdown, can significantly inhibit 4T1 xenograft tumor growth, metastasis, and osteolytic lesions in vivo. Our study demonstrates that Atp6v1c1 may promote breast cancer growth and bone metastasis through regulation of lysosomal V-ATPase activity, indicating that Atp6v1c1 may be a viable target for breast cancer therapy and silencing of Atp6v1c1 may be an innovative therapeutic approach for the treatment and prevention of breast cancer growth and metastasis.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Neoplasm Metastasis  ISOAtp6v1c1 (Mus musculus)14700647; 14700647associated with Mammary Neoplasms and ExperimentalRGD 
Neoplasm Metastasis  IMP 14700647associated with Mammary Neoplasms and ExperimentalRGD 

Objects Annotated

Genes (Rattus norvegicus)
Atp6v1c1  (ATPase H+ transporting V1 subunit C1)

Genes (Mus musculus)
Atp6v1c1  (ATPase, H+ transporting, lysosomal V1 subunit C1)

Genes (Homo sapiens)
ATP6V1C1  (ATPase H+ transporting V1 subunit C1)


Additional Information