ArticleCancer discovery2015
INPP4B Is a PtdIns(3,4,5)P3 Phosphatase That Can Act as a Tumor Suppressor.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 81 citations in OpenAlex.
- Non-redundant roles of the phosphoinositide phosphatases PTEN and PIPP in PI3K/AKT signaling in breast cancer.Communications biology · 2025Article
- Physical activity decreases cancer burden by alleviating immunosenescence-related inflammation and improving overall immunity.Cell reports. Medicine · 2025Article
- Exploration of Traditional Chinese Medicine Comprehensive Treatment of Triple Negative Breast Cancer Based on Molecular Pathological Mechanism.Breast cancer (Dove Medical Press) · 2025Review
- Regulation of EZH2 Expression by INPP4B in Normal Prostate and Primary Prostate Cancer.Cancers · 2023Article
- Role of inositol polyphosphate-4-phosphatase type II in oncogenesis of digestive system tumors.World journal of gastrointestinal oncology · 2023Review
- JARID2 coordinates with the NuRD complex to facilitate breast tumorigenesis through response to adipocyte-derived leptin.Cancer communications (London, England) · 2023Article
- The mechanisms of class 1A PI3K and Wnt/β-catenin coupled signaling in breast cancer.Biochemical Society transactions · 2023Review
- Attenuated cerebellar phenotypes in Inpp4a truncation mutants with preserved phosphatase activity.Disease models & mechanisms · 2023Article
- Tumor Suppressor Role of INPP4B in Chemoresistant Retinoblastoma.Journal of oncology · 2023Article
- Decreased INPP5B expression predicts poor prognosis in lung adenocarcinoma.Cancer cell international · 2022Article
- INPP4B inhibits glioma cell proliferation and immune escapeFrontiers in oncology · 2022Article
- Macrophages play a role in inflammatory transformation of colorectal cancer.World journal of gastrointestinal oncology · 2021Review
- INPP4B promotes PI3Kα-dependent late endosome formation and Wnt/β-catenin signaling in breast cancer.Nature communications · 2021Article
- INPP4B protects from metabolic syndrome and associated disorders.Communications biology · 2021Article
- PTEN and Other PtdIns(3,4,5)PInternational journal of molecular sciences · 2020Review
- Estrogen receptor β regulates AKT activity through up-regulation of INPP4B and inhibits migration of prostate cancer cell line PC-3.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The INPP4B Tumor Suppressor Modulates EGFR Trafficking and Promotes Triple-Negative Breast Cancer.Cancer discovery · 2020Article
- The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling.International journal of molecular sciences · 2020Review
- Proteomic analysis enables distinction of early- versus advanced-stage lung adenocarcinomas.Clinical and translational medicine · 2020Article
- PI(3,4)P2 Signaling in Cancer and Metabolism.Frontiers in oncology · 2020Review
Corrections and comments
- Commented on by
Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledInositol polyphosphate 4-phosphatase B (INPP4B) has been identified as a tumor suppressor mutated in human breast, ovary, and prostate cancers. The molecular mechanism underlying INPP4B's tumor-suppressive role is currently unknown. Here, we demonstrate that INPP4B restrains tumor development by dephosphorylating the PtdIns(3,4,5)P3 that accumulates in situations of PTEN deficiency. In vitro, INPP4B directly dephosphorylates PtdIns(3,4,5)P3. In vivo, neither inactivation of Inpp4b (Inpp4b(Δ/Δ)) nor heterozygous deletion of Pten (Pten(+/-)) in mice causes thyroid abnormalities, but a combination of these mutations induces malignant thyroid cancers with lung metastases. At the molecular level, simultaneous deletion of Inpp4b and Pten synergistically increases PtdIns(3,4,5)P3 levels and activates AKT downstream signaling proteins in thyroid cells. We propose that the PtdIns(3,4,5)P3 phosphatase activity of INPP4B can function as a "back-up" mechanism when PTEN is deficient, making INPP4B a potential novel therapeutic target for PTEN-deficient or PIK3CA-activated cancers. SIGNIFICANCE: Although INPP4B expression is reduced in several types of human cancers, our work on Inpp4B-deficient mice provides the first evidence that INPP4B is a bona fide tumor suppressor whose function is particularly important in situations of PTEN deficiency. Our biochemical data demonstrate that INPP4B directly dephosphorylates PtdIns(3,4,5)P3.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.