Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO, USA.
Cell Cycle. 2011 Dec 1;10(23):4119-27. doi: 10.4161/cc.10.23.18287.
Complement 1q-Binding Protein (C1qbp) is a mitochondrial protein reported to be upregulated in cancer. However, whether C1qbp plays a tumor suppressive or tumorigenic role in the progression of cancer is controversial. Moreover, the exact effects of C1qbp on cell proliferation, migration, and death/survival have not been definitely proven. To this end, we comprehensively examined the effects of C1qbp on mitochondrial-dependent cell death, proliferation, and migration in both normal and breast cancer cells using genetic gain- and loss-of-function approaches. In normal fibroblasts, overexpression of C1qbp protected the cells against staurosporine-induce apoptosis, increased proliferation, decreased cellular ATP, and increased cell migration in a wound-healing assay. In contrast, the opposite effects were observed in fibroblasts depleted of C1qbp by RNA interference. C1qbp expression was found to be markedly elevated in 4 different human breast cancer cell lines as well as in ductal and adenocarcinoma tumors from breast cancer patients. Stable knockdown of C1qbp by shRNA in the aggressive MDA-MB-231 breast cancer cell line greatly reduced cell proliferation, increased ATP levels, and decreased cell migration compared to control shRNA-transfected cells. Moreover, C1qbp knockdown elicited a significant increase in doxorubicin-induced apoptosis in the MDA-MB-231 cells. Finally, C1qbp upregulation was not restricted to breast cancer cells and tumors, as levels of C1qbp were also found to be significantly elevated in both human lung and colon cancer cell lines and carcinomas. Together, these results establish a pro-tumor, rather than anti-tumor, role for C1qbp, and indicate that C1qbp could serve as a molecular target for cancer therapeutics.
补体 1q 结合蛋白（C1qbp）是一种报道在癌症中上调的线粒体蛋白。然而，C1qbp 在癌症进展中是发挥肿瘤抑制还是致癌作用仍存在争议。此外，C1qbp 对细胞增殖、迁移和死亡/存活的确切影响尚未得到明确证实。为此，我们使用遗传增益和缺失功能方法全面研究了 C1qbp 对正常和乳腺癌细胞中线粒体依赖性细胞死亡、增殖和迁移的影响。在正常成纤维细胞中，C1qbp 的过表达可保护细胞免受 staurosporine 诱导的凋亡，增加增殖，减少细胞内 ATP，并增加划痕愈合试验中的细胞迁移。相比之下，用 RNA 干扰耗尽 C1qbp 的成纤维细胞则观察到相反的效果。C1qbp 的表达在 4 种不同的人乳腺癌细胞系以及来自乳腺癌患者的导管癌和腺癌肿瘤中明显升高。在侵袭性 MDA-MB-231 乳腺癌细胞系中，通过 shRNA 稳定敲低 C1qbp 与对照 shRNA 转染细胞相比，大大降低了细胞增殖，增加了 ATP 水平，并减少了细胞迁移。此外，C1qbp 敲低可显著增加 MDA-MB-231 细胞中阿霉素诱导的凋亡。最后，C1qbp 的上调不仅限于乳腺癌细胞和肿瘤，因为在人肺癌和结肠癌细胞系和癌中也发现 C1qbp 的水平明显升高。总之，这些结果确立了 C1qbp 的促肿瘤作用，而不是抗肿瘤作用，并表明 C1qbp 可以作为癌症治疗的分子靶标。
