LDH-A promotes malignant progression via activation of epithelial-to-mesenchymal transition and conferring stemness in muscle-invasive bladder cancer

Jiang, Fujin; Ma, Shenglin; Xue, Yu; Hou, Jianquan; Zhang, Yongjie

doi:10.1016/j.bbrc.2015.12.078

Cited by 59 publications

(48 citation statements)

References 18 publications

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“…LDHA suppressed epithelial phenotype and promoted mesenchymal transition. Limited investigation attempted to elucidate that LDHA could promote EMT in muscle-invasive bladder cancer (25). In the current study, retrospective analyses showed that LDHA expression was related to tumor Table I.…”

Section: Knockdown Of Ldha Inhibits Tumor Metastasis In Vivomentioning

confidence: 80%

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LDHA promotes tumor metastasis by facilitating epithelial-mesenchymal transition in renal cell carcinoma

Zhao

Huang

et al. 2017

Molecular Medicine Reports

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Previous studies have indicated that high expression of lactate dehydrogenase A (LDHA) exists in many human cancers. Recently, several reports showed that silencing or inhibition of LDHA could suppress metastasis of human cancer including renal cell carcinoma (RCC). However, the mechanism remains unknown. The role of LDHA in RCC migration and invasion was investigated using immunohistochemistry, western blotting, Transwell and scratch assays, and in vivo experiment. The influence of LDHA on the Warburg effect was also investigated by LDHA activity and lactate production assay. LDHA was overexpressed in RCC tissues and predicted a worse survival following renal resection. Correlation analysis demonstrated that LDHA was negatively correlated with E‑cadherin and positively with N‑cadherin. Experimentally, both in vivo and in vitro experiments found downregulation of LDHA suppressed RCC cells migration and invasion by inhibiting EMT. In addition, results indicated LDHA could promote the Warburg effect. Further research presented that the LDHA inhibitor, oxamate, suppressed tumor metastasis by inhibiting LDHA activity and EMT. These results demonstrated that LDHA mediates tumor metastasis by promoting EMT in RCC, suggesting that LDHA could be a promising therapeutic target for RCC therapy.

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Section: Knockdown Of Ldha Inhibits Tumor Metastasis In Vivomentioning

confidence: 80%

“…Piva et al (24) reported that EMT contributed to RCC development and progression. Jiang et al (25) reported that LDHA was elevated in muscle-invasive bladder cancer, promoting malignant progression via activation of EMT. The above findings prompted us to investigate the effects of LDHA in EMT process in RCC.…”

Section: Introductionmentioning

confidence: 99%

LDHA promotes tumor metastasis by facilitating epithelial-mesenchymal transition in renal cell carcinoma

Zhao

Huang

et al. 2017

Molecular Medicine Reports

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“…Hence, altered expression of LDHC could be involved in maintaining an alternative energy source by contributing to the metabolic switch in cancer cells. In addition, increased LDHA and decreased LDHB expressions facilitate tumor formation and progression through remodeling of the tumor microenvironment, increasing proliferation, and inducing epithelial-to-mesenchymal transition, cell migration and invasion, and angiogenesis [10][11][12][13][14][15][16][17][18][19][20]. In line with this, two studies to date demonstrate that enhanced expression of LDHC induces epithelial-to-mesenchymal transition, matrix metalloproteinase-9 (MMP9) expression and promotes cancer cell migration and invasion [7,21].…”

Section: Introductionmentioning

confidence: 82%

Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy

Thomas

Shaath

Belič

et al. 2020

Cancer Immunol Immunother

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Lactate dehydrogenase C (LDHC) is an archetypical cancer testis antigen with limited expression in adult tissues and reexpression in tumors. This restricted expression pattern together with the important role of LDHC in cancer metabolism renders LDHC a potential target for immunotherapy. This study is the first to investigate the immunogenicity of LDHC using T cells from healthy individuals. LDHC-specific T cell responses were induced by in vitro stimulation with synthetic peptides, or by priming with autologous peptide-pulsed dendritic cells. We evaluated T cell activation by IFN-γ ELISpot and determined cytolytic activity of HLA-A*0201-restricted T cells in breast cancer cell co-cultures. In vitro T cell stimulation induced IFN-γ secretion in response to numerous LDHC-derived peptides. Analysis of HLA-A*0201 responses revealed a significant T cell activation after stimulation with peptide pools 2 (PP2) and 8 (PP8). The PP2-and PP8-specific T cells displayed cytolytic activity against breast cancer cells with endogenous LDHC expression within a HLA-A*0201 context. We identified peptides LDHC 41−55 and LDHC 288−303 from PP2 and PP8 to elicit a functional cellular immune response. More specifically, we found an increase in IFN-γ secretion by CD8 + T cells and cancer-cell-killing of HLA-A*0201/LDHC positive breast cancer cells by LDHC 41−55-and LDHC 288−303-induced T cells, albeit with a possible antigen recognition threshold. The majority of induced T cells displayed an effector memory phenotype. To conclude, our findings support the rationale to assess LDHC as a targetable cancer testis antigen for immunotherapy, and in particular the HLA-A*0201 restricted LDHC 41-55 and LDHC 288-303 peptides within LDHC.

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“…Furthermore, activating epithelial‐to‐mesenchymal transition (EMT) also underlies LDHA contribution to cancer metastasis . In bladder cancer, Jiang et al found that knockdown of LDHA prevented invasion of cancer cells, accompanied by decreased Snail, N‐cadherin, fibronectin, and vimentin expression but increased E‐cadherin expression.…”

Section: Ldha In Cancer Biologymentioning

confidence: 99%

Lactate dehydrogenase A: A key player in carcinogenesis and potential target in cancer therapy

et al. 2018

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Elevated glycolysis remains a universal and primary character of cancer metabolism, which deeply depends on dysregulated metabolic enzymes. Lactate dehydrogenase A (LDHA) facilitates glycolytic process by converting pyruvate to lactate. Numerous researches demonstrate LDHA has an aberrantly high expression in multiple cancers, which is associated with malignant progression. In this review, we summarized LDHA function in cancer research. First, we gave an introduction of structure, location, and basic function of LDHA. Following, we discussed the transcription and activation mode of LDHA. Further, we focused on the function of LDHA in cancer bio‐characteristics. Later, we discussed the clinical practice of LDHA in cancer prevention and treatment. What we discussed gives a precise insight into LDHA especially in cancer research, which will contribute to exploring cancer pathogenesis and its handling measures.

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LDH-A promotes malignant progression via activation of epithelial-to-mesenchymal transition and conferring stemness in muscle-invasive bladder cancer

Cited by 59 publications

References 18 publications

LDHA promotes tumor metastasis by facilitating epithelial-mesenchymal transition in renal cell carcinoma

LDHA promotes tumor metastasis by facilitating epithelial-mesenchymal transition in renal cell carcinoma

Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy

Lactate dehydrogenase A: A key player in carcinogenesis and potential target in cancer therapy

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