title: PI(3,4)P2plays critical roles in the regulation of focal adhesion dynamics of MDA-MB-231 breast cancer cells.
abstract: Phosphoinositides play pivotal roles in the regulation of cancer cell phenotypes. Among them, phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) localizes to the invadopodia, and positively regulates tumor cell invasion. In this study, we examined the effect of PI(3,4)P2on focal adhesion dynamics in MDA-MB-231 basal breast cancer cells. Knockdown of SHIP2, a phosphatidylinositol 3,4,5-trisphosphatase (PIP3) 5-phosphatase that generates PI(3,4)P2, in MDA-MB-231 breast cancer cells, induced the development of focal adhesions and cell spreading, leading to the suppression of invasion. In contrast, knockdown of PTEN, a 3-phosphatase that de-phosphorylates PIP3and PI(3,4)P2, induced cell shrinkage and increased cell invasion. Interestingly, additional knockdown of SHIP2 rescued these phenotypes. Overexpression of the TAPP1 PH domain, which binds to PI(3,4)P2, and knockdown of Lpd, a downstream effector of PI(3,4)P2, resulted in similar phenotypes to those induced by SHIP2 knockdown. Taken together, our results suggest that inhibition of PI(3,4)P2generation and/or downstream signaling could be useful for inhibiting breast cancer metastasis.
authors.affiliation: The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Fukumoto
authors.affiliation: Division of Biochemistry, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takeshi
authors.identifier: http://orcid.org/0000-0002-0618-1776
authors.initials: T
authors.lastname: Ijuin
authors.affiliation: Division of Molecular and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D005260:Female; D022001:Focal Adhesions / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D010716:Phosphatidylinositols; C118301:phosphoinositide-3,4-bisphosphate; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Cell invasion; Lpd; PI(3,4)P2; SHIP2; focal adhesion