ArticleThe Journal of biological chemistry2015
Activated α2-macroglobulin binding to human prostate cancer cells triggers insulin-like responses.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Human α2-Macroglobulin: Architecture, Mechanisms, and Functional Implications.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Intracellular Signaling Regulated by Activated αInternational journal of molecular sciences · 2026Review
- Prognostic significance of alpha-2-macrglobulin and low-density lipoprotein receptor-related protein-1 in various cancers.American journal of cancer research · 2024Article
- Glycolysis-cholesterol metabolic axis in immuno-oncology microenvironment: emerging role in immune cells and immunosuppressive signaling.Cell & bioscience · 2023Review
- Integrating Proteomics and Lipidomics for Evaluating the Risk of Breast Cancer Progression: A Pilot Study.Biomedicines · 2023Article
- Cryo-EM structures reveal the dynamic transformation of human alpha-2-macroglobulin working as a protease inhibitor.Science China. Life sciences · 2022Article
- ER residential chaperone GRP78 unconventionally relocalizes to the cell surface via endosomal transport.Cellular and molecular life sciences : CMLS · 2021Article
- The vital role of ATP citrate lyase in chronic diseases.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Discrimination of normal oral mucosa from oral cancer by mass spectrometry imaging of proteins and lipids.Journal of molecular histology · 2019Article
- Increased Reticulon 3 (RTN3) Leads to Obesity and Hypertriglyceridemia by Interacting With Heat Shock Protein Family A (Hsp70) Member 5 (HSPA5).Circulation · 2018Article
- Ovostatin 2 knockdown significantly inhibits the growth, migration, and tumorigenicity of cutaneous malignant melanoma cells.PloS one · 2018Article
- Autoantibodies against the cell surface-associated chaperone GRP78 stimulate tumor growth via tissue factor.The Journal of biological chemistry · 2017Article
- Cell surface GRP78 promotes tumor cell histone acetylation through metabolic reprogramming: a mechanism which modulates the Warburg effect.Oncotarget · 2017Article
- SUMO-specific protease 3 is a key regulator for hepatic lipid metabolism in non-alcoholic fatty liver disease.Scientific reports · 2016Article
- Fatostatin blocks ER exit of SCAP but inhibits cell growth in a SCAP-independent manner.Journal of lipid research · 2016Article
- Rh2E2, a novel metabolic suppressor, specifically inhibits energy-based metabolism of tumor cells.Oncotarget · 2016Article
- GRP78 and α2-macroglobulin are new promising targets for metastatic castrate-resistant prostate cancer treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2015Article
- The NMDA receptor functions independently and as an LRP1 co-receptor to promote Schwann cell survival and migration.Journal of cell science · 2015Article
- The role of c-Src in the invasion and metastasis of hepatocellular carcinoma cells induced by association of cell surface GRP78 with activated α2M.BMC cancer · 2015Article
- Alpha-2-Macroglobulin Is Acutely Sensitive to Freezing and Lyophilization: Implications for Structural and Functional Studies.PloS one · 2015Article
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2 authors.
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Abstract
Ligation of cell surface GRP78 by activated α2-macroglobulin (α2M*) promotes cell proliferation and suppresses apoptosis. α2M*-treated human prostate cancer cells exhibit a 2-3-fold increase in glucose uptake and lactate secretion, an effect similar to insulin treatment. In both α2M* and insulin-treated cells, the mRNA levels of SREBP1-c, SREBP2, fatty-acid synthase, acetyl-CoA carboxylase, ATP citrate lyase, and Glut-1 were significantly increased together with their protein levels, except for SREBP2. Pretreatment of cells with α2M* antagonist antibody directed against the carboxyl-terminal domain of GRP78 blocks these α2M*-mediated effects, and silencing GRP78 expression by RNAi inhibits up-regulation of ATP citrate lyase and fatty-acid synthase. α2M* induces a 2-3-fold increase in lipogenesis as determined by 6-[(14)C]glucose or 1-[(14)C]acetate incorporation into free cholesterol, cholesterol esters, triglycerides, free fatty acids, and phosphatidylcholine, which is blocked by inhibitors of fatty-acid synthase, PI 3-kinase, mTORC, or an antibody against the carboxyl-terminal domain of GRP78. We also assessed the incorporation of [(14)CH3]choline into phosphatidylcholine and observed similar effects. Lipogenesis is significantly affected by pretreatment of prostate cancer cells with fatostatin A, which blocks sterol regulatory element-binding protein proteolytic cleavage and activation. This study demonstrates that α2M* functions as a growth factor, leading to proliferation of prostate cancer cells by promoting insulin-like responses. An antibody against the carboxyl-terminal domain of GRP78 may have important applications in prostate cancer therapy.
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