Correlation between the Warburg effect and progression of triple-negative breast cancer DOI Creative Commons
Shaojun Liu, Yuxuan Li, Meng Yuan

и другие.

Frontiers in Oncology, Год журнала: 2023, Номер 12

Опубликована: Янв. 27, 2023

Triple-negative breast cancer (TNBC) is ineligible for hormonal therapy and Her-2-targeted due to the negative expression of estrogen receptor, progesterone human epidermal growth factor receptor-2. Although targeted immunotherapy have been shown attenuate aggressiveness TNBC partially, few patients benefited from them. The conventional treatment remains chemotherapy. Chemoresistance, however, impedes therapeutic progress over time, chemotherapy toxicity increases burden on patients. Therefore, introducing more advantageous options a necessity. Metabolic reprogramming centered glucose metabolism considered hallmark tumors. It described as tumor cells tend convert lactate even under normoxic conditions, phenomenon known Warburg effect. Similar Darwinian evolution, its emergence attributed selective pressures formed by hypoxic microenvironment pre-malignant lesions. Of note, effect does not disappear with changes in after formation malignant phenotypes. Instead, it forms constitutive mediated mutations or epigenetic modifications, providing robust survival advantage primary metastatic Expanding evidence has demonstrated that mediates multiple invasive behaviors TNBC, including proliferation, metastasis, recurrence, immune escape, multidrug resistance. Moreover, effect-targeted testified be feasible inhibiting progression. However, all TNBCs are sensitive glycolysis inhibitors because flexibly switch their metabolic patterns cope different pressures, namely plasticity. Between medicines actual curative effect, plasticity creates divide must continuously researched bridged.

Язык: Английский

Thyroid hormones inhibit tumor progression and enhance the antitumor activity of lenvatinib in hepatocellular carcinoma via reprogramming glucose metabolism DOI Creative Commons

Chun‐Cheng Yang,

Yu‐Chuan Yan,

Guo‐Qiang Pan

и другие.

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Март 8, 2025

Abstract Thyroid hormones (THs) dysfunctions have been demonstrated to be associated with the risk of developing different types cancers. The role THs in regulating hepatocellular carcinoma (HCC) progression is still controversial. We that T3 can inhibit HCC by enhancing expression THRSP. Mechanistically, activate tumor suppressor LKB1/AMPK/Raptor signaling as well oncogenic PI3K/Akt HCC. Interestingly, T3-induced THRSP augment activation signaling, yet activation, thereby preventing mTOR-induced nuclear translocation HIF-1α, and ultimately suppressing ENO2-induced glycolysis progression. More importantly, exogenous enhances antitumor effect multikinase inhibitor lenvatinib vitro vivo glycolysis. Our findings reveal mechanism glucose metabolism provide new potential therapeutic strategies for treatment drug resistance reversal.

Язык: Английский

Процитировано

1
Lactate accumulation induces H4K12la to activate super-enhancer-driven RAD23A expression and promote niraparib resistance in ovarian cancer DOI Creative Commons
Bingfeng Lu, Shuo Chen,

Xue Guan

и другие.

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Март 19, 2025

Ovarian cancer is a gynecological malignancy with the highest recurrence and mortality rates. Although niraparib can effectively affect its progression, challenge of drug resistance remains. Herein, niraparib-resistant ovarian cell lines were constructed to identify abnormally activated enhancers associated target genes via RNA in situ conformation sequencing. Notably, gene RAD23A was markedly upregulated cells, inhibiting restored their sensitivity. Additionally, abnormal activation glycolysis cells induced lactate accumulation, which promoted lactylation histone H4K12 lysine residues. Correlation analysis showed that key enzymes such as pyruvate kinase M dehydrogenase A significantly positively correlated expression cancer. H4K12la super-enhancer (SE) MYC transcription factor, thereby enhancing DNA damage repair ability promoting cells. Overall, findings this study indicate lactic acid accumulation leads H4K12la, upregulating SE-mediated suggesting potential therapeutic for

Язык: Английский

Процитировано

1
PSAT1 impairs ferroptosis and reduces immunotherapy efficacy via GPX4 hydroxylation DOI

Peixiang Zheng,

Z. Hu, Shen Yu-li

и другие.

Nature Chemical Biology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

Язык: Английский

Процитировано

1
Therapeutic targeting of glutamate dehydrogenase 1 that links metabolic reprogramming and Snail-mediated epithelial–mesenchymal transition in drug-resistant lung cancer DOI Creative Commons

Qizhi Wang,

Ming Wu,

Haobin Li

и другие.

Pharmacological Research, Год журнала: 2022, Номер 185, С. 106490 - 106490

Опубликована: Окт. 8, 2022

Acquired drug resistance and epithelial-mesenchymal transition (EMT) mediated metastasis are two highly interacting determinants for non-small-cell lung cancer (NSCLC) prognosis. This study investigated the common mechanisms of EMT from perspective metabolic reprogramming, which may offer new ideas to improve anticancer therapy. resistant cells were found grow faster have a greater migratory invasive capacity than their parent cells. Metabolomics analysis revealed that acquired relied on glutamine utilization mainly fluxed into oxidative phosphorylation energy production. Further mechanistic studies screened out glutamate dehydrogenase 1 (GLUD1) as determinant addiction in NSCLC cells, provided evidence GLUD1-mediated α-KG production accompanying reactive oxygen species (ROS) accumulation primarily triggered migration invasion by inducing Snail. Pharmacological genetic interference with GLUD1 vitro significantly reversed decreased cell capability. Lastly, successful application R162, selective inhibitor, overcome both EMT-induced vivo, identified promising druggable therapeutic target malignant progression NSCLC. Collectively, our offers potential strategy therapy, especially drug-resistant patients expressed GLUD1.

Язык: Английский

Процитировано

30
Correlation between the Warburg effect and progression of triple-negative breast cancer DOI Creative Commons
Shaojun Liu, Yuxuan Li, Meng Yuan

и другие.

Frontiers in Oncology, Год журнала: 2023, Номер 12

Опубликована: Янв. 27, 2023

Triple-negative breast cancer (TNBC) is ineligible for hormonal therapy and Her-2-targeted due to the negative expression of estrogen receptor, progesterone human epidermal growth factor receptor-2. Although targeted immunotherapy have been shown attenuate aggressiveness TNBC partially, few patients benefited from them. The conventional treatment remains chemotherapy. Chemoresistance, however, impedes therapeutic progress over time, chemotherapy toxicity increases burden on patients. Therefore, introducing more advantageous options a necessity. Metabolic reprogramming centered glucose metabolism considered hallmark tumors. It described as tumor cells tend convert lactate even under normoxic conditions, phenomenon known Warburg effect. Similar Darwinian evolution, its emergence attributed selective pressures formed by hypoxic microenvironment pre-malignant lesions. Of note, effect does not disappear with changes in after formation malignant phenotypes. Instead, it forms constitutive mediated mutations or epigenetic modifications, providing robust survival advantage primary metastatic Expanding evidence has demonstrated that mediates multiple invasive behaviors TNBC, including proliferation, metastasis, recurrence, immune escape, multidrug resistance. Moreover, effect-targeted testified be feasible inhibiting progression. However, all TNBCs are sensitive glycolysis inhibitors because flexibly switch their metabolic patterns cope different pressures, namely plasticity. Between medicines actual curative effect, plasticity creates divide must continuously researched bridged.

Язык: Английский

Процитировано

20