AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling

Li, Jia; Guo, Yuanwei; Duan, Lili; Hu, Xinglin; Zhang, Xi; Hu, Jian; Huang, Li; He, Rongzhang; Hu, Zheng; Luo, Weihao; Tan, Tan; Huang, Renbin; Liao, Duan‐Fang; Zhu, Yuan‐Shan; Luo, Dixian

doi:10.18632/oncotarget.16624

Cited by 73 publications

(54 citation statements)

References 14 publications

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“…The data presented here demonstrates that AKR1B10 expression is elevated in ERand HER2+ breast cancers and that within these breast cancer subtypes, high AKR1B10 expression is associated with an increased incidence of metastatic relapse at secondary sites. In contrast to previous reports 29, 30 , we find that AKR1B10 High breast cancer cells do not display altered survival or proliferation properties when cultured in vitro in full medium ( Fig. 2c, Fig.…”

Section: Discussioncontrasting

confidence: 99%

Metabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation

Weverwijk

Koundouros

Iravani

et al. 2018

Preprint

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Running title: Regulation of fatty acid oxidation during breast cancer metastasis Keywords: breast cancer metastasis, metabolic regulation, AKR1B10, fatty acid oxidation, lung metastasis Abstract The different stages of the metastatic cascade present distinct metabolic challenges to tumour cells and an altered tumour metabolism associated with successful metastatic colonisation provides a therapeutic vulnerability in disseminated disease. We identify the aldo-keto reductase AKR1B10 as a metastasis enhancer that has little impact on primary tumour growth or dissemination but promotes effective tumour growth in secondary sites and, in human disease, is associated with an increased risk of distant metastatic relapse. AKR1B10 High tumour cells have reduced glycolytic capacity and dependency on glucose as fuel source but increased utilisation of fatty acid oxidation. Conversely, in both 3D tumour spheroid assays and in vivo metastasis assays, inhibition of fatty acid oxidation blocks AKR1B10 Highenhanced metastatic colonisation with no impact on AKR1B10 Low cells. Finally, mechanistic analysis supports a model in which AKR1B10 serves to limit the toxic side effects of oxidative stress thereby sustaining fatty acid oxidation in metabolically challenging metastatic environments.A defining characteristic of primary tumour cells is an ability to alter their metabolism, which provides the energy and metabolites required to sustain survival in nutrient and oxygen limiting conditions. In disseminating tumour cells this need for an altered metabolism becomes more acute, as cells have to avoid anoikis-mediated cell death in the circulation and face the challenge of surviving at the metastatic site before establishment of a productive metastatic colony. Moreover, different metastatic sites pose distinct metabolic challenges to the tumour cell 1,2 . In breast cancers, these altered metabolic dependencies are now being defined but the molecular mechanisms regulating this metabolic adaptability have yet to be identified.Here we report the analysis of a syngeneic in vivo RNAi screen to identify putative metastasis enhancers. Among the top hits from the screen was the aldo-keto

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Section: Discussioncontrasting

confidence: 99%

Metabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation

Weverwijk

Koundouros

Iravani

et al. 2018

Preprint

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“…To confirm the effect of miR-19-3p on HCT116 cell migration and invasion ability, the transwell assays were further carried out as the protocols reported previously. 13,14 Before experiment, 24-well transwell chambers (8 mm pore size, 6.5 mm diameter; Corning, NY, USA) were placed in 24-well plates. For cell migration assays, 5 Â 10 4 transfected cells within free-FBS medium were seeded onto the upper chamber, combined with the 10% FBS-supplemented culture medium added into the lower chamber.…”

Section: Cell Migration and Invasion Assaysmentioning

confidence: 99%

RETRACTED: MiR-19-3p Induces Tumor Cell Apoptosis via Targeting FAS in Rectal Cancer Cells

Su¹,

Zang

Wang

et al. 2020

Technol Cancer Res Treat

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MicroRNAs are reported as a vital important factor in cancer cell initiation and progression processes. MicroRNA-19-3p has drawn the attention of many researchers in recent years because of its wide expression and its key role in serious kinds of tumor cells. However, the detailed mechanism of microRNA-19a-3p in these tumors is still poorly understood. So, in the present study, we aimed to explore the biological function and potential molecular mechanism of microRNA-19a-3p in different cancer cells. We first detect the relative level of miR-19a-3p in cancer cell lines and tumor tissues compared to normal cells and tissues. Results indicated the messenger RNA expression of microRNA-19a-3p existing in an aberrant low level in cancer cells and tissues. The overexpression of microRNA-19a-3p significantly reduced the cell proliferation, migration, and invasion ability in HCT116 cells. In addition to this, increased microRNA-19a-3p could induce cell apoptosis via promoting reactive oxygen species (ROS) accumulation, whereas inhibition of microRNA-19a-3p exhibited an opposite effect. Moreover, we predicated the target genes and the binding sites of microRNA-19a-3p and confirmed FAS as the targeting of microRNA-19a-3p through luciferase activity assay. Taken together, these results indicated that microRNA-19a-3p overexpression inhibited HCT116 cell proliferation, migration and invasion, induced cell apoptosis, and ROS accumulation via FAS targeting effect. It was conceivable that microRNA-19a-3p might serve as a potential molecular target for breast and liver cancer treatment.

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“…Thus, AKR1B10 may regulate proliferation-related and EMTrelated proteins via the PI3K/AKT/NF-κB signaling cascade. Another study has shown that AKR1B10 can promote proliferation and migration/invasion of breast cancer cells via the ERK and FAK/Src/Rac1 signaling pathway [8,32]. Several studies have also demonstrated that PI3K/AKT and MEK/ERK signaling pathways can be activated in tumors together [33][34][35].…”

Section: Discussionmentioning

confidence: 99%

“…All experiments were performed with mycoplasma-free cells. Overexpression stable cell line and knockdown stable cell line were established as previously described [8] in our laboratory. Wherever mentioned, cells were treated with 30 µM and/or 50 µM of the PI3K inhibitor LY294002 (CST) for 48 h.…”

Section: Cell Culture and Treatmentsmentioning

confidence: 99%

“…AKR1B10 plays a central role in cancer lipid metabolism by governing the synthesis of lipids through stabilizing acetyl coenzyme-A carboxylase α [6]. In recent studies, mRNA levels of AKR1B10 were detected in several types of tumors [7][8][9]. In hepatocellular carcinoma (HCC) patients, the high expression of AKR1B10 positively correlated with poor prognosis [10].…”

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confidence: 99%

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AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway

et al. 2020

Preprint

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BackgroudAberrant expression of Aldo-Keto reductase family 1 member B10 (AKR1B10) has been observed during the progression of some human carcinomas. However, the expression pattern and clinical relevance of AKR1B10 in breast cancer (BC) need clarification.MethodsThe relationship between the high expression of AKR1B10 and the overall prognosis and disease-free survival of breast cancer patients was analyzed by Kaplan-Meier Plotter database. Breast cancer cell lines MCF-7/AKR1B10 stably overexpressing AKR1B10 and breast cancer cell lines BT-20/shAKR1B10 that knock down AKR1B10 were constructed, respectively. RT-qPCR, Western blot and immunohistochemistry were used to detect the expression of AKR1B10 in breast cancer and its normal tissues. CCK8 cell proliferation assay and cell scratch test were used to detect the proliferation and migration of breast cancer cells. Western blot was used to detect the expression of proliferation-related proteins cyclinD1, c-myc, survivin and EMT-related proteins twist, snail, slug, ZEB1, E-cadherin, PI3K, p-PI3K, AKT, p-AKT, IKBα, p-IKBα, NF-κB p65, and p-NF-κB p65 proteins in breast cancer cells. The PI3K inhibitor LY94002 was used to treat MCF-7 cells to detect PI3K/AKT/NF-κB signal cascade protein Expression, and expression of NF-κB p65 in nucleoproteins and plasma proteins.ResultsIn this study, we found that AKR1B10 expression was higher in BC tissue compared to paired non-cancerous tissue. The expression of AKR1B10 positively correlated with lymph node metastasis, tumor size, Ki67 expression, and p53 expression, but inversely correlated with overall and disease-free survival rates. Gene Ontology (GO) analysis showed that AKR1B10 was closely related to cell proliferation. Overexpression of AKR1B10 facilitated proliferation and migration of BC cells in vitro in association with induction of epithelial-mesenchymal transition. Conversely, knockdown of AKR1B10 inhibited these effects. Mechanistically, silencing AKR1B10 reduced the phosphorylation of PI3K, AKT, and NF-κB p65, whereas AKR1B10 overexpression activated these signaling molecules. Indeed, PI3K inhibition attenuated NF-κB p65 nuclear localization.ConclusionsOur results demonstrate that AKR1B10 promotes proliferation and migration of BC cells and represents a novel prognostic indicator as well as a potential therapeutic target in BC.

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AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling

Cited by 73 publications

References 14 publications

Metabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation

Metabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation

RETRACTED: MiR-19-3p Induces Tumor Cell Apoptosis via Targeting FAS in Rectal Cancer Cells

AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway

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