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.

Original publication

DOI

10.1371/journal.pone.0015581

Type

Journal article

Journal

PloS one

Publication Date

30/12/2010

Volume

5

Addresses

Functional Genomics and Computational Biology Group, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States America.

Keywords

Epithelial Cells, Humans, Breast Neoplasms, Colorectal Neoplasms, Cell Transformation, Neoplastic, Disease Progression, Adaptor Proteins, Signal Transducing, Antineoplastic Agents, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Apoptosis, Gene Expression Regulation, Neoplastic, Gene Silencing, RNA Interference, Female