ArticleCancer discovery2015
In Vivo Role of INPP4B in Tumor and Metastasis Suppression through Regulation of PI3K-AKT Signaling at Endosomes.
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 59 papers.
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Who cites it
59 citing papers in PubMed, 98 citations in OpenAlex.
- PI(3,5)PScience advances · 2026Article
- Non-redundant roles of the phosphoinositide phosphatases PTEN and PIPP in PI3K/AKT signaling in breast cancer.Communications biology · 2025Article
- Androgen deprivation-mediated activation of AKT is enhanced in prostate cancer with TMPRSS2:ERG fusion.The Journal of clinical investigation · 2025Article
- Upregulation of miR-151a-5p in high DFI sperm induces DNA damage and mitochondrial dysfunction by targeting INPP4B and VAMP1.Reproductive biology and endocrinology : RB&E · 2025Article
- Endosomal HAntioxidants (Basel, Switzerland) · 2025Article
- PTPN23-dependent activation of PI3KC2α is a therapeutic vulnerability of BRAF-mutant cancers.The Journal of experimental medicine · 2025Article
- INPP4B promotes PDAC aggressiveness via PIKfyve and TRPML-1-mediated lysosomal exocytosis.The Journal of cell biology · 2024Article
- VASH2 enhances KIF3C-mediated EGFR-endosomal recycling to promote aggression and chemoresistance of lung squamous cell carcinoma by increasing tubulin detyrosination.Cell death & disease · 2024Article
- [Preliminary Study of the Role of INPP4B in Promoting Colorectal Cancer Metastasis and the Mechanisms Involved].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Article
- The mechanisms of class 1A PI3K and Wnt/β-catenin coupled signaling in breast cancer.Biochemical Society transactions · 2023Review
- Fructose utilization enhanced by GLUT5 promotes lung cancer cell migration via activating glycolysis/AKT pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Tumor Suppressor Role of INPP4B in Chemoresistant Retinoblastoma.Journal of oncology · 2023Article
- Expression patterns and the roles of phosphatidylinositol phosphatases in testis†.Biology of reproduction · 2022Article
- Endosome maturation links PI3Kα signaling to lysosome repopulation during basal autophagy.The EMBO journal · 2022Article
- INPP4B inhibits glioma cell proliferation and immune escapeFrontiers in oncology · 2022Article
- JPX and LINC00641 ncRNAs expression in prostate tissue: a case-control study.Research in pharmaceutical sciences · 2021Article
- Thyroid Hormone Receptor Beta as Tumor Suppressor: Untapped Potential in Treatment and Diagnostics in Solid Tumors.Cancers · 2021Review
- Thyroid Hormone Receptor Beta Inhibits PI3K-Akt-mTOR Signaling Axis in Anaplastic Thyroid Cancer via Genomic Mechanisms.Journal of the Endocrine Society · 2021Article
- INPP4B promotes PI3Kα-dependent late endosome formation and Wnt/β-catenin signaling in breast cancer.Nature communications · 2021Article
- Taxifolin Targets PI3K and mTOR and Inhibits Glioblastoma Multiforme.Journal of oncology · 2021Article
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16 authors at 4 institutions in 3 countries.
Funding
Abstract
unlabelledThe phosphatases PTEN and INPP4B have been proposed to act as tumor suppressors by antagonizing PI3K-AKT signaling and are frequently dysregulated in human cancer. Although PTEN has been extensively studied, little is known about the underlying mechanisms by which INPP4B exerts its tumor-suppressive function and its role in tumorigenesis in vivo. Here, we show that a partial or complete loss of Inpp4b morphs benign thyroid adenoma lesions in Pten heterozygous mice into lethal and metastatic follicular-like thyroid cancer (FTC). Importantly, analyses of human thyroid cancer cell lines and specimens reveal INPP4B downregulation in FTC. Mechanistically, we find that INPP4B, but not PTEN, is enriched in the early endosomes of thyroid cancer cells, where it selectively inhibits AKT2 activation and in turn tumor proliferation and anchorage-independent growth. We therefore identify INPP4B as a novel tumor suppressor in FTC oncogenesis and metastasis through localized regulation of the PI3K-AKT pathway at the endosomes. SIGNIFICANCE: Although both PTEN and INPP4B can inhibit PI3K-AKT signaling through their lipid phosphatase activities, here we demonstrate lack of an epistatic relationship between the two tumor suppressors. Instead, the qualitative regulation of PI3K-AKT2 signaling by INPP4B provides a mechanism for their cooperation in suppressing thyroid tumorigenesis and metastasis.
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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.