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

Huang, Chenfei; Cao, Zhe; Ma, Jun; Shen, Yi; Bu, Yiwen; Khoshaba, Ramina; Shi, Guiyuan; Huang, Dan; Liao, Duan‐Fang; Ji, Haitao; Jin, Junfei; Cao, Deliang

doi:10.1002/mc.22844

Cited by 37 publications

(39 citation statements)

References 42 publications

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“…(42)(43)(44) In lung cancer, AKR1B10 is up-regulated in non-small cell lung carcinoma in smokers, (42) and in breast cancer, AKR1B10 promotes cancer growth and progression by promoting lipogenesis and lipid messenger-mediated signaling cascades and thus is a potential therapeutic target. (43,45) In conclusion, our study demonstrates that serum AKR1B10 can differentiate HCC from HCs, BLTs, and high-HCC-risk chronic hepatitis and cirrhosis with high accuracy. AKR1B10 also has privilege in detection of early-stage HCC and AFP-negative HCC.…”

Section: Discussionmentioning

confidence: 58%

“…AKR1B10 expression and potential as a biomarker is also reported in other tumors, such as lung, breast, and pancreatic cancers . In lung cancer, AKR1B10 is up‐regulated in non–small cell lung carcinoma in smokers, and in breast cancer, AKR1B10 promotes cancer growth and progression by promoting lipogenesis and lipid messenger‐mediated signaling cascades and thus is a potential therapeutic target …”

Section: Discussionmentioning

confidence: 85%

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A Large‐Scale Multicenter Study Validates Aldo‐Keto Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of Hepatocellular Carcinoma

et al. 2019

Hepatology

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Aldo‐keto reductase family 1 member B10 (AKR1B10) is a secretory protein overexpressed in hepatocellular carcinoma (HCC). We aimed to evaluate AKR1B10 as a serum marker for detection of HCC. Herein, we conducted a cohort study that consecutively enrolled 1,244 participants from three independent hospitals, including HCC, healthy controls (HCs), benign liver tumors (BLTs), chronic hepatitis B (CHB), and liver cirrhosis (LC). Serum AKR1B10 was tested by time‐resolved fluorescent assays. Data were plotted for receiver operating characteristic (ROC) curve analyses. Alpha‐fetoprotein (AFP) was analyzed for comparison. An exploratory discovery cohort demonstrated that serum AKR1B10 increased in patients with HCC (1,567.3 ± 292.6 pg/mL; n = 69) compared with HCs (85.7 ± 10.9 pg/mL; n = 66; P < 0.0001). A training cohort of 519 participants yielded an optimal diagnostic cutoff of serum AKR1B10 at 267.9 pg/mL. When ROC curve was plotted for HCC versus all controls (HC + BLT + CHB + LC), serum AKR1B10 had diagnostic parameters of the area under the curve (AUC) 0.896, sensitivity 72.7%, and specificity 95.7%, which were better than AFP with AUC 0.816, sensitivity 65.1%, and specificity 88.9%. Impressively, AKR1B10 showed promising diagnostic potential in early‐stage HCC and AFP‐negative HCC. Combination of AKR1B10 with AFP increased diagnostic accuracy for HCC compared with AKR1B10 or AFP alone. A validation cohort of 522 participants confirmed these findings. An independent cohort of 68 patients with HCC who were followed up showed that serum AKR1B10 dramatically decreased 1 day after operation and was nearly back to normal 3 days after operation. Conclusion : AKR1B10 is a potent serum marker for detection of HCC and early‐stage HCC, with better diagnostic performance than AFP.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 85%

A Large‐Scale Multicenter Study Validates Aldo‐Keto Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of Hepatocellular Carcinoma

et al. 2019

Hepatology

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“…For example, cPLA2α has been shown to mediate EMT via the PI3K/AKT pathway [29]. Previous studies suggest that PIP 2 is upregulated in BC cells in which AKR1B10 is overexpressed [6], which prompted us to investigate the phosphatidylinositol and PI3K/AKT pathway in detail. Consistently, our study demonstrated that the PI3K/AKT pathway was up-regulated in AKR1B10-induced BC progression.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, AKR1B10 has been reported to regulate phosphatidylinositol (3, 4)-bisphosphate (PIP 2 ) expression in BC cells [6]. PIP 2 is the substrate of phosphatidylinositol 3-kinase (PI3K) [16].…”

Section: Akr1b10 Activates Pi3k/akt Pathwaymentioning

confidence: 99%

“…Aldo-Keto reductase family 1 member B10 (AKR1B10), also known as Aldose reductase like protein-1 (ARL-1), is a member of the human aldo-keto reductase (AKR) superfamily which protects cells by reducing aldehyde ketone carbonyl compounds to alcohols [5]. 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].…”

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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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Serum AKR1B10 as an indicator of unfavorable survival of hepatocellular carcinoma

et al. 2023

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

Cited by 37 publications

References 42 publications

A Large‐Scale Multicenter Study Validates Aldo‐Keto Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of Hepatocellular Carcinoma

A Large‐Scale Multicenter Study Validates Aldo‐Keto Reductase Family 1 Member B10 as a Prevalent Serum Marker for Detection of Hepatocellular Carcinoma

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

Serum AKR1B10 as an indicator of unfavorable survival of hepatocellular carcinoma

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