The Inositol Polyphosphate 5-Phosphatase PIPP Regulates AKT1-Dependent Breast Cancer Growth and Metastasis

Ooms, Lisa M; Binge, Lauren Clare; Davies, Elizabeth M.; Rahman, Parvin; Conway, James R. W.; Gurung, Rajendra; Ferguson, Daniel T.; Papa, Antonella; Fedele, Clare G.; Vieusseux, Jessica L.; Chai, Ryan C.; Köentgen, Frank; Price, John T.; Tiganis, Tony; Timpson, Paul; McLean, Catriona; Mitchell, Christina A.

doi:10.1016/j.ccell.2015.07.003

Cited by 97 publications

(113 citation statements)

References 55 publications

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“…The use of protein domains for the detection of phosphoinositides as biosensors has been reported in previous studies (Davies et al, 2014;Ooms et al, 2015). Fluorescence intensity has been determined in N1 vector control cells or N1shSHIP2 cells transfected with GFP-PH-PLCδ1, used as a probe for PI(4,5)P2 (Stauffer et al, 1998).…”

Section: Lowering Ship2 Expression Potentiated Cell Migration In N1 Gmentioning

confidence: 98%

“…In breast cancer cells, the inositol polyphosphate 5-phosphatase synaptojanin 2 promotes cell migration and invasion in culture but also lung metastasis of breast tumor xenografts in mice (Ben-Chetrit et al, 2015). In another study, depletion of the proline-rich inositol polyphosphate 5-phosphatase PIPP (also known as INPP5J) has been shown to increase transformation and accelerate oncogene-driven tumor growth in vivo, whereas paradoxically reducing cell migration, invasion and metastasis (Ooms et al, 2015); this study identifies PIPP as a suppressor of oncogenic PI3K signaling in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma cells

Edimo

Ghosh

Derua

et al. 2016

Journal of Cell Science

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Phosphoinositides, particularly phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3] and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], are recognized by SHIP2 (also known as INPPL1) a member of the inositol polyphosphate 5-phosphatase family. SHIP2 dephosphorylates PI(3,4,5)P3 to form PI(3,4)P2; the latter interacts with specific target proteins (e.g. lamellipodin). Although the preferred SHIP2 substrate is PI(3,4,5)P3, PI(4,5)P2 can also be dephosphorylated by this enzyme to phosphatidylinositol 4-phosphate (PI4P). Through depletion of SHIP2 in the glioblastoma cell line 1321 N1, we show that SHIP2 inhibits cell migration. In different glioblastoma cell lines and primary cultures, SHIP2 staining at the plasma membrane partly overlaps with PI(4,5)P2 immunoreactivity. PI(4,5)P2 was upregulated in SHIP2-deficient N1 cells as compared to control cells; in contrast, PI4P was very much decreased in SHIP2-deficient cells. Therefore, SHIP2 controls both PI(3,4,5)P3 and PI(4,5)P2 levels in intact cells. In 1321 N1 cells, the PI(4,5)P2-binding protein myosin-1c was identified as a new interactor of SHIP2. Regulation of PI(4,5)P2 and PI4P content by SHIP2 controls 1321 N1 cell migration through the organization of focal adhesions. Thus, our results reveal a new role of SHIP2 in the control of PI(4,5)P2, PI4P and cell migration in PTEN-deficient glioblastoma 1321 N1 cells.

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Section: Lowering Ship2 Expression Potentiated Cell Migration In N1 Gmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma cells

Edimo

Ghosh

Derua

et al. 2016

Journal of Cell Science

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“…Extensive efforts have been made towards a better understanding of human breast cancer oncogenic events, and many biomarkers have been reported to be an indicator for initiation and invasion of breast cancer. These may include among others; proline rich inositol polyphosphate 5-phosphatase (PIPP), which when depleted inhibits PI3K/AKT signaling, enhanced the transformation ability of breast cancer cells, but reduced cell migration and invasion thus indicating that PIPP is a potential suppressor of oncogenic PI3K/AKT signaling in breast cancer (8); bone marrow stromal antigen 2 which is expressed in cancer cells and facilitates the emergence of neoplasia and malignant progression of breast cancer (9) and others such as oncoprotein hepatitis B X-interacting protein which when mediated by general control non-derepressible 5 promotes the migration of breast cancer cells and therapeutically could act as a novel target in breast cancer (10).…”

Section: Introductionmentioning

confidence: 99%

PEG10 promotes human breast cancer cell proliferation, migration and invasion

Xiao

Tembo

et al. 2016

International Journal of Oncology

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Abstract. Paternally expressed imprinted gene 10 (PEG10), derived from the Ty3/Gypsy family of retrotransposons, has been implicated as a genetic imprinted gene. Accumulating evidence suggests that PEG10 plays an important role in tumor growth in various cancers, including hepatocellular carcinoma, lung cancer and prostate cancer. However, the correlation between PEG10 and breast cancer remains unclear.In the present study, we evaluated and characterized the role of PEG10 in human breast cancer proliferation, cell cycle, clone formation, migration and invasion. The expression level of PEG10 was significantly elevated in breast cancer tissues and associated with distant metastasis and poor clinical outcome. Gene set enrichment analysis indicated that high expression of PEG10 could enrich cell cycle-related processes in breast cancer tissues. Ectopic overexpression of PEG10 in breast cancer cells enhanced cell proliferation, cell cycle, clone formation along with migration and invasion. Cell-to-cell junction molecule E-cadherin was downregulated and matrix degradation proteases MMP-1, MMP-2, MMP-9 were up regulated after PEG10 overexpression. Our results demonstrated that PEG10 is a crucial oncogene and has prognostic value for breast cancer, which could be applied in breast cancer diagnosis and targeting therapy in future.

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“…Overactivation of AKT signaling can also induce the upregulation of NFATC1 and further promote osteoclastogenesis [36]. At the same time, overactivation of AKT can also promote tumor proliferation and migration [35,37,38]. Our results indicated that GCTSC-secreted CCL20 could significantly induce the overactivation of both the AKT and NF-κB pathways during osteoclast differentiation.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 69%

Stromal Cell-Derived CCL20 Promotes Tumor Progression and Osteolysis in Giant Cell Tumor of Bone

Zhao

Wang

Tang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Giant cell tumor of bone (GCTB), one of the most common primary bone tumors, leads to extensive bone destruction. However, the mechanisms underlying GCTB progression remain elusive and prognostic factors and treatment targets are required. In the current study, we explored the function of the chemokine family member CCL20 in GCTB progression. Methods: We explored the expression of CCL20 in stromal cells (GCTSCs) using microarray. Clinical analyses of the role of CCL20 in tumor progression were performed based on the patient cohort of our institution. The role of CCL20 in tumor proliferation was evaluated by MTS assay, migration ability was measured by a Transwell assay, and osteoclastogenesis was induced by CCL20 or GCTSC-conditioned medium. Quantitative PCR and western blot were used to measure the expression levels of mRNAs and proteins related to tumor progression. Results: CCL20 was upregulated in GCTSCs and correlated with tumor progression and prognosis. CCL20 induced GCTSC proliferation and migration in an autocrine manner. In addition, CCL20 recruited mononuclear cells and induced osteoclastogenesis by overactivating the AKT and NF-κB signaling pathways. Antibody blockade of CCL20 abolished the exacerbated osteoclastogenesis. Conclusion: Taken together, our data indicate that GCTSC secretion of CCL20 acts as a key modulator in the pathological progression of GCTB. It can promote GCTSC proliferation and migration in an autocrine manner and can recruit bone marrow monocytes to the tumor microenvironment and enhance osteoclastogenesis in a paracrine manner. These findings strongly indicate the potential prognostic and therapeutic value of CCL20 in GCTB.

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The Inositol Polyphosphate 5-Phosphatase PIPP Regulates AKT1-Dependent Breast Cancer Growth and Metastasis

Cited by 97 publications

References 55 publications

SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma cells

SHIP2 controls plasma membrane PI(4,5)P2 thereby participating in the control of cell migration in 1321 N1 glioblastoma cells

PEG10 promotes human breast cancer cell proliferation, migration and invasion

Stromal Cell-Derived CCL20 Promotes Tumor Progression and Osteolysis in Giant Cell Tumor of Bone

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