title: A fibrillar form of fibronectin induces apoptosis by activating SHP-2 and stress fiber formation.
abstract: Fibronectin (FN) is an endogenous ligand of integrins, which plays a critical role in cell adhesion and growth. Here, we converted globular FN (G-FN) into a fibrillar form (F-FN) and found that, even though both G-FN and F-FN interacted with integrin alpha5beta1, G-FN induced cellular proliferation, whereas F-FN resulted in apoptosis that was associated with deactivation of Akt/GSK-3beta and phosphorylation of SHP-2. SHP-2 inhibitor and anti-sense oligodeoxynucleotide decreased SHP-2 level and reversed the F-FN mediated apoptosis. F-FN also induced stress fiber formation associated with activation of RhoA, Rho kinase (ROCK), and filamin. Inhibition of ROCK by ROCK inhibitor or dominant negative plasmid treatment modulated F-FN mediated apoptosis. Pharmacological studies revealed that F-FN was effective in inhibiting the survival of SKOV-3 and MCF-7 cancer cells. These findings thus demonstrate that unlike G-FN, F-FN exhibits fibrillar structure to induce cell apoptosis that is associated with phosphorylation of SHP-2, activation of RhoA/ROCK and formation of stress fibers as well as deactivation of Akt/GSK-3beta.
authors.affiliation: Institute of Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chun-Yung
authors.initials: CY
authors.lastname: Huang
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Liang
authors.forename: Chiao-Li
authors.initials: CL
authors.lastname: Chu
authors.forename: Jei-Ming
authors.initials: JM
authors.lastname: Peng
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Liang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D006801:Humans; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism*; D022502:Stress Fibers / Q000378:metabolism* / Q000648:ultrastructure; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D005353:Fibronectins; D054460:rho-Associated Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11