title: Targeting ILK and β4 integrin abrogates the invasive potential of ovarian cancer.
abstract: Integrins and integrin-linked kinase (ILK) are essential to cancerous invasion because they mediate physical interactions with the extracellular matrix, and regulate oncogenic signaling pathways. The purpose of our study is to determine whether deletion of β1 and β4 integrin and ILK, alone or in combination, has antitumoral effects in ovarian cancer. Expression of β1 and β4 integrin and ILK was analyzed by immunohistochemistry in 196 ovarian cancer tissue samples. We assessed the effects of depleting these molecules with shRNAs in ovarian cancer cells by Western blot, conventional RT-PCR, cell proliferation, migration, invasion, and in vitro Rac1 activity assays, and in vivo xenograft formation assays. Overexpression of β4 integrin and ILK in human ovarian cancer specimens was found to correlate with tumor aggressiveness. Depletion of these targets efficiently suppresses ovarian cancer cell proliferation, migration, and invasion in vitro and xenograft tumor formation in vivo. We also demonstrated that single depletion of ILK or combination depletion of β4 integrin/ILK inhibits phosphorylation of downstream signaling targets, p-Ser 473 Akt and p-Thr202/Tyr204 Erk1/2, and activation of Rac1, as well as reduce expression of MMP-2 and MMP-9 and increase expression of caspase-3 in vitro. In conclusion, targeting β4 integrin combined with ILK can instigate the latent tumorigenic potential and abrogate the invasive potential in ovarian cancer.
authors.affiliation: BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yoon Pyo
authors.initials: YP
authors.lastname: Choi
authors.forename: Baek Gil
authors.initials: BG
authors.lastname: Kim
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Gao
authors.forename: Suki
authors.initials: S
authors.lastname: Kang
authors.forename: Nam Hoon
authors.initials: NH
authors.lastname: Cho
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D005260:Female; D018390:Gene Targeting; D016147:Genes, Tumor Suppressor; D006801:Humans; D039663:Integrin beta4 / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D000099200:Scaffold Protein ILK
chemical_list: D039663:Integrin beta4; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000099200:Scaffold Protein ILK