&lt;p&gt;FAM46B Promotes Apoptosis and Inhibits Glycolysis of Prostate Cancer Through Inhibition of the MYC-LDHA Axis&lt;/p&gt;

Tao, Liang; Ye, Xuxiao; Yan, Dongming; Deng, Chuiwen; Li, Zuowei; Tian, Baohong

doi:10.2147/ott.s258724

Cited by 12 publications

(8 citation statements)

References 32 publications

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“…These variances could also be seen in the response of LDHA , as it was only downregulated in LXF-289 cells but not in BKZ-6 or BKZ-8. In pancreatic and prostate cancer, a correlation of MYC with LDHA expression was detected and linked to the regulation of aerobic glycolysis while promoting tumor progression and decreasing apoptosis [ 67 , 72 ]. Thus, downregulation of LDHA may be one cause for KJ-Pyr-9-mediated decrease in cell survival of LXF-289.…”

Section: Discussionmentioning

confidence: 99%

Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer: Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling

Windmöller

Beshay²,

Helweg

et al. 2021

Cells

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There is growing evidence that cancer stem cells (CSCs), a small subpopulation of self-renewal cancer cells, are responsible for tumor growth, treatment resistance, and cancer relapse and are thus of enormous clinical interest. Here, we aimed to isolate new CSC-like cells derived from human primary non-small cell lung cancer (NSCLC) specimens and to analyze the influence of different inhibitors of NF-κB and MYC signaling on cell survival. CSC-like cells were established from three squamous cell carcinomas (SCC) and three adenocarcinomas (AC) of the lung and were shown to express common CSC markers such as Prominin-1, CD44-antigen, and Nestin. Further, cells gave rise to spherical cancer organoids. Inhibition of MYC and NF-κB signaling using KJ-Pyr-9, dexamethasone, and pyrrolidinedithiocarbamate resulted in significant reductions in cell survival for SCC- and AC-derived cells. However, inhibition of the protein–protein interaction of MYC/NMYC proto-oncogenes with Myc-associated factor X (MAX) using KJ-Pyr-9 revealed the most promising survival-decreasing effects. Next to the establishment of six novel in vitro models for studying NSCLC-derived CSC-like populations, the presented investigations might provide new insights into potential novel therapies targeting NF-κB/MYC to improve clinical outcomes in NSCLC patients. Nevertheless, the full picture of downstream signaling still remains elusive.

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Section: Discussionmentioning

confidence: 99%

Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer: Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling

Windmöller

Beshay²,

Helweg

et al. 2021

Cells

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“…The regulation of LDHA expression through the Wnt/β-catenin signaling pathway was also found in this study. LDHA catalyzes lactate production, and glycolysis is one of the basic characteristics of tumor cell metabolism [ 23 , 24 ]. Upon producing lactate, tumor cells quickly obtain intermediate materials for ATP and biomacromolecule synthesis, reshaping the tumor microenvironment [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma

Zhong

Chen

et al. 2021

Cell Death Dis

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Aberrant activation of Wnt/β-catenin signaling and dysregulation of metabolism have been frequently observed in lung cancer. However, the molecular mechanism by which Wnt/β-catenin signaling is regulated and the link between Wnt/β-catenin signaling and cancer metabolism are not fully understood. In this study, we showed that the loss of dual serine/threonine tyrosine protein kinase (DSTYK) led to the activation of Wnt/β-catenin signaling and upregulation of its target gene, lactate dehydrogenase (LDHA), and thus the elevation of lactate. DSTYK phosphorylated the N-terminal domain of β-catenin and inhibited Wnt/β-catenin signaling, which led to the inhibition of cell growth, colony formation and tumorigenesis in a lung adenocarcinoma mouse model. DSTYK was downregulated in lung cancer tissues, and its expression was positively correlated with the survival of patients with lung adenocarcinoma. Taken together, these results demonstrate that the loss of DSTYK activates Wnt/β-catenin/LDHA signaling to promote the tumorigenesis of lung cancer and that DSTYK may be a therapeutic target.

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“…Aerobic glycolysis is the most important energy metabolism which allows cancer cells to meet energy and substances requirements for proliferation [ 13 ], and it is the main consequence of the aberrant activation of oncogenes like c–MYC , mTOR , and HIF–1α [ 14 , 15 , 16 ]. c–MYC promotes the aerobic glycolytic process by facilitating the transcription of target genes such as glucose transporter 1 ( GLUT1 ) and lactate dehydrogenase A ( LDHA ) [ 17 , 18 ]. c–MYC mRNA was found down–regulated upon CLDN6 overexpression according to our previous RNAseq data of MCF–7 cells, but the validation and exploration of relevant mechanisms are still needed.…”

Section: Introductionmentioning

confidence: 99%

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

Wang

et al. 2021

IJMS

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Claudin 6 (CLDN6) was found to be a breast cancer suppressor gene, which is lowly expressed in breast cancer and inhibits breast cancer cell proliferation upon overexpression. However, the mechanism by which CLDN6 inhibits breast cancer proliferation is unclear. Here, we investigated this issue and elucidated the molecular mechanisms by which CLDN6 inhibits breast cancer proliferation. First, we verified that CLDN6 was lowly expressed in breast cancer tissues and that patients with lower CLDN6 expression had a worse prognosis. Next, we confirmed that CLDN6 inhibited breast cancer proliferation through in vitro and in vivo experiments. As for the mechanism, we found that CLDN6 inhibited c–MYC–mediated aerobic glycolysis based on a metabolomic analysis of CLDN6 affecting cellular lactate levels. CLDN6 interacted with a transcriptional co–activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c–MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c–MYC–mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer.

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<p>FAM46B Promotes Apoptosis and Inhibits Glycolysis of Prostate Cancer Through Inhibition of the MYC-LDHA Axis</p>

Cited by 12 publications

References 32 publications

Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer: Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling

Novel Primary Human Cancer Stem-Like Cell Populations from Non-Small Cell Lung Cancer: Inhibition of Cell Survival by Targeting NF-κB and MYC Signaling

Loss of DSTYK activates Wnt/β-catenin signaling and glycolysis in lung adenocarcinoma

CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

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