Functional Genomics and Computational Biology Group, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States America.
PLoS One. 2010 Dec 30;5(12):e15581. doi: 10.1371/journal.pone.0015581.
GIPC1 is a cytoplasmic scaffold protein that interacts with numerous receptor signaling complexes, and emerging evidence suggests that it plays a role in tumorigenesis. GIPC1 is highly expressed in a number of human malignancies, including breast, ovarian, gastric, and pancreatic cancers. Suppression of GIPC1 in human pancreatic cancer cells inhibits in vivo tumor growth in immunodeficient mice. To better understand GIPC1 function, we suppressed its expression in human breast and colorectal cancer cell lines and human mammary epithelial cells (HMECs) and assayed both gene expression and cellular phenotype. Suppression of GIPC1 promotes apoptosis in MCF-7, MDA-MD231, SKBR-3, SW480, and SW620 cells and impairs anchorage-independent colony formation of HMECs. These observations indicate GIPC1 plays an essential role in oncogenic transformation, and its expression is necessary for the survival of human breast and colorectal cancer cells. Additionally, a GIPC1 knock-down gene signature was used to interrogate publically available breast and ovarian cancer microarray datasets. This GIPC1 signature statistically correlates with a number of breast and ovarian cancer phenotypes and clinical outcomes, including patient survival. Taken together, these data indicate that GIPC1 inhibition may represent a new target for therapeutic development for the treatment of human cancers.
GIPC1 是一种细胞质支架蛋白，可与许多受体信号复合物相互作用，新出现的证据表明它在肿瘤发生中起作用。GIPC1 在许多人类恶性肿瘤中高度表达，包括乳腺癌、卵巢癌、胃癌和胰腺癌。在人胰腺癌细胞中抑制 GIPC1 可抑制免疫缺陷小鼠体内的肿瘤生长。为了更好地了解 GIPC1 的功能，我们抑制了人乳腺癌和结直肠癌细胞系以及人乳腺上皮细胞（HMEC）中的 GIPC1 表达，并检测了基因表达和细胞表型。GIPC1 的抑制可促进 MCF-7、MDA-MD231、SKBR-3、SW480 和 SW620 细胞的凋亡，并损害 HMEC 锚定非依赖性集落形成。这些观察结果表明 GIPC1 在致癌转化中起着至关重要的作用，其表达对于人乳腺癌和结直肠癌细胞的存活是必需的。此外，还使用 GIPC1 敲低基因特征来分析公共可用的乳腺癌和卵巢癌微阵列数据集。该 GIPC1 特征与许多乳腺癌和卵巢癌表型和临床结局（包括患者生存）具有统计学相关性。总之，这些数据表明 GIPC1 抑制可能代表治疗人类癌症的治疗开发的新靶点。
