HKDC1 promotes the tumorigenesis and glycolysis in lung adenocarcinoma via regulating AMPK/mTOR signaling pathway

Wang, Xinyu; Shi, Bowen; Zhao, Yue; Lu, Qijue; Fei, Xiang; Lu, Chaojing; Li, Chunguang; Chen, Hezhong

doi:10.1186/s12935-020-01539-7

Cited by 42 publications

(24 citation statements)

References 34 publications

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“…mTOR is an important regulator of cell metabolism. Studies have demonstrated that mTOR-mediated glycolysis plays an important role in the tumor cell proliferation and migration 30 , 31 . Therefore, we suspect that mTOR may be the hinge that links CD36 to glycolysis.…”

Section: Resultsmentioning

confidence: 99%

The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis

et al. 2021

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Metabolic reprogramming is a new hallmark of cancer but it remains poorly defined in hepatocellular carcinogenesis (HCC). The fatty acid receptor CD36 is associated with both lipid and glucose metabolism in the liver. However, the role of CD36 in metabolic reprogramming in the progression of HCC still remains to be elucidated. In the present study, we found that CD36 is highly expressed in human HCC as compared with non-tumor hepatic tissue. CD36 overexpression promoted the proliferation, migration, invasion, and in vivo tumor growth of HCC cells, whereas silencing CD36 had the opposite effects. By analysis of cell metabolic phenotype, CD36 expression showed a positive association with extracellular acidification rate, a measure of glycolysis, instead of oxygen consumption rate. Further experiments verified that overexpression of CD36 resulted in increased glycolysis flux and lactic acid production. Mechanistically, CD36 induced mTOR-mediated oncogenic glycolysis via activation of Src/PI3K/AKT signaling axis. Pretreatment of HCC cells with PI3K/AKT/mTOR inhibitors largely blocked the tumor-promoting effect of CD36. Our findings suggest that CD36 exerts a stimulatory effect on HCC growth and metastasis, through mediating aerobic glycolysis by the Src/PI3K/AKT/mTOR signaling pathway.

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Section: Resultsmentioning

confidence: 99%

The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis

et al. 2021

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“…Aberrational expression of HKDC1 is associated with various cancers, including colorectal cancer [ 25 ], liver cancer [ 26 ], and breast cancer [ 27 ]. Additionally, Wang and his colleagues reported that HKDC1 was overexpressed in LUAD tissues, and high expression of HKDC1 promoted proliferation, migration, and invasion in LUAD [ 28 ]. Thus, HKDC1 can serve as a prognostic biomarker for LUAD patients [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, Wang and his colleagues reported that HKDC1 was overexpressed in LUAD tissues, and high expression of HKDC1 promoted proliferation, migration, and invasion in LUAD [ 28 ]. Thus, HKDC1 can serve as a prognostic biomarker for LUAD patients [ 28 ]. The aldehyde dehydrogenase (ALDH) superfamily comprises 19 enzymes that play a vital role in maintaining epithelial homeostasis.…”

Section: Discussionmentioning

confidence: 99%

A glycolysis-based three-gene signature predicts survival in patients with lung squamous cell carcinoma

et al. 2021

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Background Lung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes. Although numerous biomarkers have been found to be associated with prognosis in LUSC, the prediction effect of a single gene biomarker is insufficient, especially for glycolysis-related genes. Therefore, we aimed to develop a novel glycolysis-related gene signature to predict survival in patients with LUSC. Methods The mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset. Results Based on Gene Set Enrichment Analysis (GSEA), we found 5 glycolysis-related gene sets that were significantly enriched in LUSC tissues. Univariate and multivariate Cox proportional regression models were performed to choose prognostic-related gene signatures. Based on a Cox proportional regression model, a risk score for a three-gene signature (HKDC1, ALDH7A1, and MDH1) was established to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis indicated that the risk score for this three-gene signature can be used as an independent prognostic indicator in LUSC. Additionally, based on the cBioPortal database, the rate of genomic alterations in the HKDC1, ALDH7A1, and MDH1 genes were 1.9, 1.1, and 5% in LUSC patients, respectively. Conclusion A glycolysis-based three-gene signature could serve as a novel biomarker in predicting the prognosis of patients with LUSC and it also provides additional gene targets that can be used to cure LUSC patients.

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“…Recent studies indicate that HKDC1 has an oncogenic function in specific cancer types by different mechanisms, such as liver cancer [ 19 ], breast cancer [ 20 ], lymphoma [ 27 ], colorectal cancer [ 28 ], and lung cancer [ 29 ]. HKDC1 was proven to be substantially expressed in lung adenocarcinoma (LUAD) tissues and cell lines, and a correlation between HKDC1 positive expression with an aggressive phenotype and a poor prognosis in LUAD patients was found by Wang et al HKDC1 overexpression accelerated glycolysis, proliferation, invasion, migration, EMT, and tumorigenicity, while knockdown of HKDC1 had the opposite functional consequences [ 30 ]. From the study of Chen et al, both clinical tumor tissues and breast cancer cells have high levels of HKDC1 expression.…”

Section: Discussionmentioning

confidence: 99%

Type XXVIII Collagen Regulates Renal Interstitial Fibrosis and Epithelial-Mesenchymal Transition by SREBP1-Mediated HKDC1 Expression

Zou

et al. 2022

J Renin Angiotensin Aldosterone Syst

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Background. A novel collagen called type XXVIII collagen (COL28) is involved in cancer and lung fibrosis. Preliminary data showed that renal tubular epithelial cells could proliferate, migrate, and undergo an epithelial-mesenchymal transition (EMT) when COL28 was overexpressed; however, it is still unknown how this occurs and what the underlying mechanism is. Methods. We analyzed the differential expression of genes (DEGs) in the stable COL28 overexpression HK-2 cell lines by RNA-sequencing analysis, before which Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) analyses were performed. Genes related to COL28 promoting HK-2 cell proliferation and EMT were screened and verified. By using western blot and immunofluorescence, the effects of COL28 on the expression of α-SMA, E-cadherin, Snail, HKDC1, and SREBP1 were detected. The effect of COL28 overexpression on renal fibrosis in unilateral ureteral obstruction (UUO) mice was detected by H&E and Masson staining. HKDC1 interference agent was synthesized and transfected into the HK-2 cell line stably overexpressing COL28. In HK-2 cells, the effects of HKDC1 interference on the expression of α-SMA, E-cadherin, and Snail were detected. Results. We screened and verified that HKDC1 was related to COL28 and promoted HK-2 cell proliferation and EMT. WB showed that in HK-2 cells, COL28 overexpression increased α-SMA, Snail, HKDC1, and SREBP1 expressions and decreased E-cadherin expression. Overexpression of COL28 aggravated renal interstitial fibrosis in UUO mice; upregulated α-SMA, Snail, HKDC1, and SREBP1 expressions; and decreased the E-cadherin protein expression in UUO mice. Interference of HKDC1 expression promoted the E-cadherin protein expression while inhibiting α-SMA, Snail, HKDC1, and SREBP1 protein expressions. Conclusion. Overexpression of COL28 can aggravate renal interstitial fibrosis by encouraging renal tubular epithelial cells to undergo EMT, and interference with HKDC1 expression can alleviate fibrosis by reversing EMT induced by COL28 overexpression.

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HKDC1 promotes the tumorigenesis and glycolysis in lung adenocarcinoma via regulating AMPK/mTOR signaling pathway

Cited by 42 publications

References 34 publications

The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis

The fatty acid receptor CD36 promotes HCC progression through activating Src/PI3K/AKT axis-dependent aerobic glycolysis

A glycolysis-based three-gene signature predicts survival in patients with lung squamous cell carcinoma

Type XXVIII Collagen Regulates Renal Interstitial Fibrosis and Epithelial-Mesenchymal Transition by SREBP1-Mediated HKDC1 Expression

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