INPP4B suppresses prostate cancer cell invasion

Hodgson, Myles C.; Deryugina, Elena I.; Suarez, Egla; Lopez, Sandra M.; Lin, Dong; Xue, Hui; Gorlov, Ivan P.; Wang, Yuzhuo; Agoulnik, Irina U.

doi:10.1186/s12964-014-0061-y

Cited by 36 publications

(16 citation statements)

References 65 publications

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“…Signaling transduced by PI(3,4)P 2 can be modulated by inositol polyphosphate 4-phosphastases type II (INPP4B), which preferentially hydrolyzes PI(3,4)P 2 to phosphatidylinositol-3-phosphate (PI(3)P) [5]. This dephosphorylation compromises the activation of AKT, which unveils the tumor-suppressing function of INPP4B in the context of some malignancies [6,7]. The model proposed by a relevant research indicates that INPP4B promotes the serum and glucocorticoid-regulated kinase 3 (SGK3)-mediated degradation of metastasis suppressor N-myc downstream regulated 1 (NDRG1) in breast cancer harboring oncogenic mutation in PIK3CA [8].…”

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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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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“…INPP4B plays an important role in cancer, and its function as a potential tumor suppressor has been documented in breast, ovarian, prostate, bladder, lung and nasopharyngeal cancer, and in melanoma . Interestingly, INPP4B negatively regulated the cell invasion capacity of prostate cancer cell lines, and altered its gene expression patterns, in a manner dependent on protein kinase C signaling, but not on phosphoinositide 3‐kinase–AKT signaling . On the other hand, INPP4B expression has been correlated with chemoresistance and poor overall survival and clinical outcome in acute myeloid leukemia .…”

Section: Class I Cys‐based Phosphatasesmentioning

confidence: 99%

The extended human PTPome: a growing tyrosine phosphatase family

2015

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Tyr phosphatases are, by definition, enzymes that dephosphorylate phospho‐Tyr (pTyr) from proteins. This activity is found in several structurally diverse protein families, including the protein Tyr phosphatase (PTP), arsenate reductase, rhodanese, haloacid dehalogenase (HAD) and His phosphatase (HP) families. Most of these families include members with substrate specificity for non‐pTyr substrates, such as phospho‐Ser/phospho‐Thr, phosphoinositides, phosphorylated carbohydrates, mRNAs, or inorganic moieties. A Cys is essential for catalysis in PTPs, rhodanese and arsenate reductase enzymes, whereas this work is performed by an Asp in HAD phosphatases and by a His in HPs, via a catalytic mechanism shared by all of the different families. The category that contains most Tyr phosphatases is the PTP family, which, although it received its name from this activity, includes Ser, Thr, inositide, carbohydrate and RNA phosphatases, as well as some inactive pseudophosphatase proteins. Here, we propose an extended collection of human Tyr phosphatases, which we call the extended human PTPome. The addition of new members (SACs, paladin, INPP4s, TMEM55s, SSU72, and acid phosphatases) to the currently categorized PTP group of enzymes means that the extended human PTPome contains up to 125 proteins, of which ~ 40 are selective for pTyr. We set criteria to ascribe proteins to the extended PTPome, and summarize the more important features of the new PTPome members in the context of their phosphatase activity and their relationship with human disease.

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“…INPP4B is expressed in ESR1-positive breast cancer cells and acts as a tumor suppressor by inhibiting mammary cell proliferation through regulation of the PI3K/Akt signaling pathway (28). INPP4B also selectively suppresses prostate cancer cell invasion by modulating androgen receptor transcriptional activity (29). Interestingly, INPP4B mRNA was significantly decreased in endometriotic stromal cells, which have inherently low ESR1 expression levels in comparison with healthy eutopic endometrium (20).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide estrogen receptor-α binding and action in human endometrial stromal cells

Yilmaz¹,

Sison²,

Yıldız³

et al. 2020

F&S Science

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Objective: To investigate the gene targets of estradiol (E2)-estrogen receptor-a (ESR1) in human endometrial stromal cells. Design: Basic science. Setting: University research center. Patient(s): Premenopausal women with or without endometriosis. Intervention(s): Primary cultures of human endometrial stromal cells from healthy endometrium, with or without small-interfering RNA (siRNA) knockdown of ESR1 expression, were treated with E2 or vehicle control. Main Outcome Measure(s): Genome-wide RNA expression by RNA sequencing was compared in endometrial stromal cells with or without siRNA knockdown of ESR1 in the presence or absence of E2. Genome-wide recruitment of ESR1 to chromatin was assessed by chromatin immunoprecipitation sequencing. Gene expression by real-time qualitative polymerase chain reaction of a potential E2-ESR1 target gene was determined in endometrial stromal cells and endometriotic stromal cells. Result(s): We identified several important pathways that are dependent on E2-ESR1 signaling in endometrial stromal cells, including progesterone signaling, cell-matrix adhesion, and cytoskeleton rearrangement, as well as paracrine signaling by members of the fibroblast growth factor family. We detected a total of 709 ESR1 target sites on chromatin. By integrating data on genome-wide transcriptomic changes and E2-ESR1 binding sites, we identified inositol polyphosphate phosphatase type II (INPP4B) as a candidate E2-mediated suppressor of proliferation in healthy endometrial cells. INPP4B was downregulated in endometriosisderived stromal cells. Conclusion(s): E2-ESR1 activates genes involved in human endometrial stromal cell cycle regulation, progesterone response, and production of stromal growth factors. Understanding the direct role of estrogen on the endometrial stroma and identifying downstream targets of E2-ESR1 can inform the development of targeted therapies for endometriosis and diminished endometrial receptivity.

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INPP4B suppresses prostate cancer cell invasion

Cited by 36 publications

References 65 publications

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

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

The extended human PTPome: a growing tyrosine phosphatase family

Genome-wide estrogen receptor-α binding and action in human endometrial stromal cells

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