Silencing of atp6v1c1 prevents breast cancer growth and bone metastasis.
Silencing of atp6v1c1 prevents breast cancer growth and bone metastasis.
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DOI：
10.7150/ijbs.6030
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发表时间：
2013
影响因子：
9.2
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Feng S;Zhu G;McConnell M;Deng L;Zhao Q;Wu M;Zhou Q;Wang J;Qi J;Li YP;Chen W
先前的研究表明，Atp6v1c1（V-ATP酶复合物的V0和V1结构域组装的调节因子）在转移性口腔肿瘤中表达上调。尽管有这些研究，Atp6v1c1 在肿瘤生长和转移中的功能仍然未知。 Atp6v1c1在转移性口腔鳞状细胞癌中的表达表明Atp6v1c1在癌症生长和转移中具有重要功能。我们假设 Atp6v1c1 的表达升高对于癌症生长和转移至关重要，并且 Atp6v1c1 通过激活 V-ATPase 活性促进癌症生长和转移。为了检验这一假设，我们采用慢病毒介导的RNAi敲低方法来研究Atp6v1c1在小鼠4T1乳腺肿瘤细胞体外增殖和迁移以及体内癌症生长和转移中的功能。我们的数据显示，4T1 癌细胞中 Atp6v1c1 的沉默会抑制溶酶体酸化，并在体外通过 Matrigel 严重损害 4T1 细胞的生长、迁移和侵袭。我们还表明，Atp6v1c1 敲低与 Lenti-c1s3（一种针对 Atp6v1c1 的 shRNA 介导敲低的慢病毒）可以显着抑制体内 4T1 异种移植肿瘤的生长、转移和溶骨性病变。我们的研究表明Atp6v1c1可能通过调节溶酶体V-ATP酶活性促进乳腺癌生长和骨转移，这表明Atp6v1c1可能是乳腺癌治疗的可行靶点，而Atp6v1c1沉默可能是治疗和预防乳腺癌生长和转移的创新治疗方法。
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.
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影响因子：
4.3
作者：
Day CP;Carter J;Bonomi C;Esposito D;Crise B;Ortiz-Conde B;Hollingshead M;Merlino G
通讯作者：
Merlino G
影响因子：
4.3
作者：
Joyce, JA;Hanahan, D
通讯作者：
Hanahan, D
影响因子：
5.8
作者：
Martínez-Zaguilán, R;Raghunand, N;Gillies, RJ
通讯作者：
Gillies, RJ
影响因子：
6.2
作者：
Iwai, Kaori;Koike, Masato;Ishii, Masaru
通讯作者：
Ishii, Masaru
影响因子：
5.8
作者：
Larkin, M. A.;Blackshields, G.;Higgins, D. G.
通讯作者：
Higgins, D. G.