title: α3β1 integrin promotes radiation-induced migration of meningioma cells.
abstract: Cell motility is influenced by the microenvironment, signal transduction and cytoskeleton rearrangement. Cancer cells become resistant to these control mechanisms and gain the ability to move throughout the body and invade healthy tissues, which leads to metastatic disease. Integrins respond to context-dependent cues and promote cell migration and survival in cancer cells. In the present study, we analyzed the role of integrins in radiation-induced migration of meningioma cells. Migration and cell proliferation assays revealed that radiation treatment (7 Gy) significantly increased migration and decreased proliferation in two cell lines, IOMM-Lee and CH-157-MN. α3 and β1 integrins were overexpressed at both the protein and transcript levels after radiation treatment and a function-blocking α3β1 antibody inhibited the radiation-induced migration. Immunofluorescence studies illustrated the localization of α3 integrin and F-actin at the migration front of irradiated cells. Further, an increase in phosphorylation of FAK and ERK was observed, while both FAK phosphorylation inhibitor and FAK shRNA inhibited ERK phosphorylation and downregulated uPA and vinculin. In addition to the co-localization of FAK and ERK at the migration front, these FAK-inhibition results link the downstream effects of ERK to FAK. Correspondingly, U0126 quenched ERK phosphorylation and reduced the expression of molecules involved in migration. Furthermore, brain sections of the animals implanted with tumors followed by radiation treatment showed elevated levels of α3 integrin and active ERK. Taken together, our results show that radiation treatment enhances the migration of meningioma cells with the involvement of α3β1 integrin-mediated signaling via FAK and ERK.
authors: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, USA.
authors: Venkateswara Rao
authors: VR
authors: Gogineni
authors: Arun Kumar
authors: AK
authors: Nalla
authors: Reshu
authors: R
authors: Gupta
authors: Meena
authors: M
authors: Gujrati
authors: Jeffrey D
authors: JD
authors: Klopfenstein
authors: Sanjeeva
authors: S
authors: Mohanam
authors: Jasti S
authors: JS
authors: Rao
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D039201:Integrin alpha3beta1 / Q000235:genetics / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D008579:Meningioma / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D021381:Protein Transport; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D048049:Extracellular Signal-Regulated MAP Kinases; D051417:Focal Adhesion Kinase 1; D039201:Integrin alpha3beta1; D019892:eIF-2 Kinase