title: Therapeutic implications of GIPC1 silencing in cancer.
abstract: 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.
authors.affiliation: Functional Genomics and Computational Biology Group, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States America.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Chittenden
authors.forename: Jane
authors.initials: J
authors.lastname: Pak
authors.forename: Renee
authors.initials: R
authors.lastname: Rubio
authors.forename: Hailing
authors.initials: H
authors.lastname: Cheng
authors.forename: Kristina
authors.initials: K
authors.lastname: Holton
authors.forename: Niall
authors.initials: N
authors.lastname: Prendergast
authors.forename: Vladimir
authors.initials: V
authors.lastname: Glinskii
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.forename: Aedin
authors.initials: A
authors.lastname: Culhane
authors.forename: Stefan
authors.initials: S
authors.lastname: Bentink
authors.forename: Mathew
authors.initials: M
authors.lastname: Schwede
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Mar
authors.forename: Eleanor A
authors.initials: EA
authors.lastname: Howe
authors.forename: Martin
authors.initials: M
authors.lastname: Aryee
authors.forename: Razvan
authors.initials: R
authors.lastname: Sultana
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Lanahan
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Taylor
authors.forename: Chris
authors.initials: C
authors.lastname: Holmes
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
authors.forename: Jean J
authors.initials: JJ
authors.lastname: Zhao
authors.forename: J Dirk
authors.initials: JD
authors.lastname: Iglehart
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D034622:RNA Interference
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C492009:GIPC1 protein, human