title: The H1047R point mutation in p110 alpha changes the morphology of human colon HCT116 cancer cells.
abstract: The class IA phosphatidylinositol 3-kinases (PI3K) is involved in controlling changes in cell morphology, which is a highly coordinated cellular event. This event is powered by actin filament polymerization and remodeling. The gain-of-function mutations in the catalytic subunit of p110α of class IA PI3K, which occur in up to one-third of human colorectal cancers (CRCs), are capable of causing dysregulation of cell signaling and thus may result in the alteration in cell morphology and motility and in turn cause cancer metastasis. In vivo studies have demonstrated that cell lines bearing the H1047R point mutation, the most frequent cancer-specific mutation in the kinase domain of p110α, are more metastatic than cells carrying wild-type p110α. In the current study, we show that the H1047R in p110α of PI3K decreases F-actin polymerization, increases the formation of filopodia and significantly changes the cell morphology in HCT116 cancer cells. The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2), which is also involved in actin polymerization and cell migration, is downregulated by the H1047R mutation in p110α. Our data suggest that the H1047R mutation in PI3K is responsible for the rearrangement of the cytoskeleton, alteration in cell morphology and enhancing cell motility, and that Bcl-2 may be involved in the H1047R mutation-mediated morphological changes and increased migratory capability.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of New Mexico , Albuquerque, NM, USA.
authors.forename: G
authors.initials: G
authors.lastname: Wan
authors.affiliation: Spatiotemporal Modeling Center, Comprehensive Cancer Center, University of New Mexico , Albuquerque, NM, USA.
authors.forename: C
authors.initials: C
authors.lastname: Pehlke
authors.affiliation: Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico , Albuquerque, NM, USA.
authors.forename: R
authors.initials: R
authors.lastname: Pepermans
authors.affiliation: Department of Molecular Genetics Microbiology, University of New Mexico , Albuquerque, NM, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Cannon
authors.affiliation: Department of Pathology, University of New Mexico , Albuquerque, NM, USA.
authors.forename: D
authors.initials: D
authors.lastname: Lidke
authors.affiliation: Division of Surgical Oncology, Department of Surgery, University of New Mexico , Albuquerque, NM, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rajput