ArticleCell death discovery2017
PHLPP regulates hexokinase 2-dependent glucose metabolism in colon cancer cells.
Article in Cell death discovery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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
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Who cites it
21 citing papers in PubMed, 82 citations in OpenAlex.
- Integrated Transcriptomics and Single-Cell RNA Sequencing Analyses Reveal the Potential Role of Obesity-Related Genes in Polycystic Ovary Syndrome.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- The Role of HK2 in Tumorigenesis and Development: Potential for Targeted Therapy with Natural Products.International journal of medical sciences · 2025Review
- PHLPP1 inhibits the growth and aerobic glycolysis activity of human ovarian granular cells through inactivating AKT pathway.BMC women's health · 2024Article
- The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer.International journal of biological sciences · 2024Review
- Inhibition of mitochondrial fission activates glycogen synthesis to support cell survival in colon cancer.Cell death & disease · 2023Article
- Activation of Drp1 promotes fatty acids-induced metabolic reprograming to potentiate Wnt signaling in colon cancer.Cell death and differentiation · 2022Article
- The metabolic enzyme hexokinase 2 localizes to the nucleus in AML and normal haematopoietic stem and progenitor cells to maintain stemness.Nature cell biology · 2022Article
- Circular RNA circRASSF5 Functions as an Anti-Oncogenic Factor in Hepatocellular Carcinoma by Acting as a Competitive Endogenous RNA Through Sponging miR-331-3p.Journal of hepatocellular carcinoma · 2022Article
- Mitochondria dysfunction in circulating tumor cells.Frontiers in oncology · 2022Review
- Downregulation of PHLPP induced by endoplasmic reticulum stress promotes eIF2α phosphorylation and chemoresistance in colon cancer.Cell death & disease · 2021Article
- Emerging roles of PHLPP phosphatases in metabolism.BMB reports · 2021Review
- Pleckstrin homology (PH) domain and Leucine Rich Repeat Phosphatase 1 (Phlpp1) Suppresses Parathyroid Hormone Receptor 1 (Pth1r) Expression and Signaling During Bone Growth.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Hexokinase 2 in Cancer: A Prima Donna Playing Multiple Characters.International journal of molecular sciences · 2021Review
- Upregulation of CPT1A is essential for the tumor-promoting effect of adipocytes in colon cancer.Cell death & disease · 2020Article
- Shear stress activates ATOH8 via autocrine VEGF promoting glycolysis dependent-survival of colorectal cancer cells in the circulation.Journal of experimental & clinical cancer research : CR · 2020Article
- Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis.Frontiers in oncology · 2020Article
- Identification of Potential Biomarkers with Diagnostic Value in Pituitary Adenomas Using Prediction Analysis for Microarrays Method.Journal of molecular neuroscience : MN · 2019Article
- The mitochondrial retrograde signaling regulates Wnt signaling to promote tumorigenesis in colon cancer.Cell death and differentiation · 2019Article
- S100A4 alters metabolism and promotes invasion of lung cancer cells by up-regulating mitochondrial complex I protein NDUFS2.The Journal of biological chemistry · 2019Article
- PIM2-mediated phosphorylation of hexokinase 2 is critical for tumor growth and paclitaxel resistance in breast cancer.Oncogene · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Increased glucose metabolism is considered as one of the most important metabolic alterations adapted by cancer cells in order to generate energy as well as high levels of glycolytic intermediates to support rapid proliferation. PH domain leucine-rich repeat protein phosphatase (PHLPP) belongs to a novel family of Ser/Thr protein phosphatases that function as tumor suppressors in various types of human cancer. Here we determined the role of PHLPP in regulating glucose metabolism in colon cancer cells. Knockdown of PHLPP increased the rate of glucose consumption and lactate production, whereas overexpression of PHLPP had the opposite effect. Bioenergetic analysis using Seahorse Extracelluar Flux Analyzer revealed that silencing PHLPP expression induced a glycolytic shift in colon cancer cells. Mechanistically, we found that PHLPP formed a complex with Akt and hexokinase 2 (HK2) in the mitochondrial fraction of colon cancer cells and knockdown of PHLPP enhanced Akt-mediated phosphorylation and mitochondrial localization of HK2. Depletion of HK2 expression or treating cells with Akt and HK2 inhibitors reversed PHLPP loss-induced increase in glycolysis. Furthermore, PHLPP knockdown cells became addicted to glucose as a major energy source in that glucose starvation significantly decreased cancer cell survival. As HK2 is the key enzyme that determines the direction and magnitude of glucose flux, our study identified PHLPP as a novel regulator of glucose metabolism by controlling HK2 activity in colon cancer cells.
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.