AKR1B10 activates diacylglycerol (DAG) second messenger in breast cancer cells

Molecular Carcinogenesis
Chenfei HuangDeliang Cao

Abstract

Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. However, little is known of the molecular mechanisms of action. Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. Our data showed that ectopic expression of AKR1B10 in breast cancer cells MCF-7 promoted lipogenesis and enhanced levels of lipid second messengers, including phosphatidylinositol bisphosphate (PIP2), diacylglycerol (DAG), and inositol triphosphate (IP3). In contrast, silencing of AKR1B10 in breast cancer cells BT-20 and colon cancer cells HCT-8 led to decrease of these lipid messengers. Qualitative analyses by liquid chromatography-mass spectrum (LC-MS) revealed that AKR1B10 regulated the cellular levels of total DAG and majority of subspecies. This in turn modulated the phosphorylation of protein kinase C (PKC) isoforms PKCδ (Thr505), PKCµ (Ser744/748), and PKCα/βII (Thr638/641) and activity of the PKC-mediated c-Raf/MEK/ERK signaling cascade. A pan inhibitor of PKC (Go6983) blocked ERK1/2 activation by AKR1B10. In these cells, phospho-p90RSK, phospho-MSK, and Cyclin D1 expression was increased by AKR1B10, and pharmacological inhibition of the ERK signaling cas...Continue Reading

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Citations

Jan 24, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xu YeDeliang Cao
Mar 2, 2021·Frontiers in Cell and Developmental Biology·Xin WangDeliang Cao
Jun 3, 2021·Metabolites·Satoshi EndoToru Nishinaka
Jul 3, 2021·Animals : an Open Access Journal From MDPI·Parichart TesenaAttawit Kovitvadhi
Jul 8, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Simone da Silva Lamartine-HanemannMarisa Ionta
May 30, 2019·ACS Central Science·Netta VidavskyLara A Estroff

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