<scp>PI</scp>(3,4)P<sub>2</sub> plays critical roles in the regulation of focal adhesion dynamics of <scp>MDA</scp>‐<scp>MB</scp>‐231 breast cancer cells

Fukumoto, Manabu; Ijuin, Takeshi; Takenawa, Tadaomi

doi:10.1111/cas.13215

Cited by 28 publications

(28 citation statements)

References 50 publications

(105 reference statements)

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“…It is known that focal adhesion assembly involves the activation of 1-integrin downstream of LPA 1 signaling; this is also decreased in LPA 1 −/− chondrocytes as compared to normal cells. The influence of the loss of SHIP2 expression on focal adhesion dynamics has also been shown in many cancer cells (Elong Edimo et al, 2016;Elong Edimo, Vanderwinden, & Erneux, 2013;Fukumoto, Ijuin, & Takenawa, 2017).…”

Section: Discussionmentioning

confidence: 85%

Fibroblasts derived from patients with opsismodysplasia display SHIP2-specific cell migration and adhesion defects

et al. 2017

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The SH2 domain containing inositol phosphatase 2 (SHIP2) dephosphorylates PI(3,4,5)P3 to generate PI(3,4)P2, a lipid involved in the control of cell migration and adhesion. The INPPL1 gene that encodes SHIP2 has been found to be mutated in several cases of opsismodysplasia (OPS), a rare autosomal recessive chondrodysplasia characterized by growth plate defects and delayed bone maturation. Reported mutations often result in premature stop codons or missense mutations in SHIP2 catalytic domain. SHIP2 biochemical properties are known from studies in cancer cells; its role in endochondral ossification is unknown. Here, we report two novel mutations in the INPPL1 gene and show that cell migration is very much decreased in fibroblasts derived from three OPS patients as compared with control individuals. In contrast, cell adhesion on fibronectin is increased in OPS fibroblasts. An inhibitory effect on migration was also observed when normal fibroblasts were incubated in the presence of a SHIP2 competitive inhibitor. We conclude that both migration and adhesion are very much disrupted in OPS-derived fibroblasts. It is suggested that signaling events linked to migration and particularly to adhesion, which are lost in OPS patients, would prevent normal endochondral ossification.

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Section: Discussionmentioning

confidence: 85%

Fibroblasts derived from patients with opsismodysplasia display SHIP2-specific cell migration and adhesion defects

et al. 2017

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“…Though localized to the Golgi apparatus, PI4P promotes tumor motility, angiogenesis, invasion, and metastasis [51]. PI(3,4)P2 has also been implicated in metastasis as its upregulation leads to an increase in invadopodia formation and loss of focal adhesions [91]. These cells also showed a significant decrease in the cell surface expression of PI3P.…”

Section: Discussionmentioning

confidence: 99%

Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer

Devanathan

Jones

Kaur

et al. 2020

IJMS

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Studies have suggested that type 2 diabetes (T2D) is associated with a higher incidence of breast cancer and related mortality rates. T2D postmenopausal women have an ~20% increased chance of developing breast cancer, and women with T2D and breast cancer have a 50% increase in mortality compared to breast cancer patients without diabetes. This correlation has been attributed to the general activation of insulin receptor signaling, glucose metabolism, phosphatidylinositol (PI) kinases, and growth pathways. Furthermore, the presence of breast cancer specific PI kinase and/or phosphatase mutations enhance metastatic breast cancer phenotypes. We hypothesized that each of the breast cancer subtypes may have characteristic PI phosphorylation profiles that are changed in T2D conditions. Therefore, we sought to characterize the PI phosphorylation when equilibrated in normal glycemic versus hyperglycemic serum conditions. Our results suggest that hyperglycemia leads to: 1) A reduction in PI3P and PIP3, with increased PI4P that is later converted to PI(3,4)P2 at the cell surface in hormone receptor positive breast cancer; 2) a reduction in PI3P and PI4P with increased PIP3 surface expression in human epidermal growth factor receptor 2-positive (HER2+) breast cancer; and 3) an increase in di- and tri-phosphorylated PIs due to turnover of PI3P in triple negative breast cancer. This study begins to describe some of the crucial changes in PIs that play a role in T2D related breast cancer incidence and metastasis.

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“…The advances achieved recently shed new light on the pivotal role of phosphatidylinositol-3,4-bisphosphate (PI (3,4)P 2 ) metabolism and signaling in the regulation of cancerous cellular events: motility and invasiveness [3,4]. Mounting evidences have established that PI(3,4) P 2 dominates a distinct by-pass of the PI3K/AKT pathway.…”

Section: Introductionmentioning

confidence: 99%

Inositol polyphosphate-4-phosphatase type II plays critical roles in the modulation of cadherin-mediated adhesion dynamics of pancreatic ductal adenocarcinomas

Zhang

Wang

et al. 2018

Cell Adhesion & Migration

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The inositol polyphosphate-4-phosphatase type II (INPP4B) has been mostly proposed to act as a tumor suppressor whose expression is frequently dysregulated in numerous human cancers. To date, little is unveiled about whether and how INPP4B will exert its tumor suppressive function on the turnover of cadherin-based cell-cell adhesion system in pancreatic ductal adenocarcinomas (PDACs) in vitro. Here we provide the evidence that INPP4B manipulates cadherin switch in certain PDAC cell lines through a phosphorylated AKT-inactivation manner. The knockdown of INPP4B in AsPC-1 results in a more invasive phenotype, and overexpression of it in PANC-1 leads to partial reversion of mesenchymal status and impediment of in vitro invasion but not migration. More importantly, E-cadherin (Ecad) is enriched in the early and sorting endosomes containing INPP4B by which its recycling rather than degradation is enabled. Immunohistochemical analysis of 39 operatively resected PDAC specimens reveals it is poorly differentiated, non-cohesive ones in which the INPP4B and Ecad are partially or completely compromised in expression. We therefore identify INPP4B as an tumor suppressor in PDAC which attenuates AKT activation and participates in preservation of Ecad in endocytic pool and cellular membrane.

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PI(3,4)P₂ plays critical roles in the regulation of focal adhesion dynamics of MDA‐MB‐231 breast cancer cells

Cited by 28 publications

References 50 publications

Fibroblasts derived from patients with opsismodysplasia display SHIP2-specific cell migration and adhesion defects

Fibroblasts derived from patients with opsismodysplasia display SHIP2-specific cell migration and adhesion defects

Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer

Inositol polyphosphate-4-phosphatase type II plays critical roles in the modulation of cadherin-mediated adhesion dynamics of pancreatic ductal adenocarcinomas

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PI(3,4)P2 plays critical roles in the regulation of focal adhesion dynamics of MDA‐MB‐231 breast cancer cells

Cited by 28 publications

References 50 publications

Fibroblasts derived from patients with opsismodysplasia display SHIP2-specific cell migration and adhesion defects

Fibroblasts derived from patients with opsismodysplasia display SHIP2-specific cell migration and adhesion defects

Using Phosphatidylinositol Phosphorylation as Markers for Hyperglycemic Related Breast Cancer

Inositol polyphosphate-4-phosphatase type II plays critical roles in the modulation of cadherin-mediated adhesion dynamics of pancreatic ductal adenocarcinomas

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PI(3,4)P₂ plays critical roles in the regulation of focal adhesion dynamics of MDA‐MB‐231 breast cancer cells