Lactate regulates cell cycle by remodelling the anaphase promoting complex

Liu, Weihai; Wang, Yun; Bozi, Luíz Henrique Marchesi; Fischer, Patrick D.; Jedrychowski, Mark P.; Xiao, Haopeng; Wu, Tao; Darabedian, Narek; He, Xinlei; Mills, Evanna L.; Burger, Nils; Shin, Sang-Hee; Reddy, Anita; Sprenger, Hans‐Georg; Tran, Nhien; Winther, Sally; Hinshaw, Stephen M.; Shen, Jingnan; Seo, Hyuk-Soo; Song, Kijun; Xu, Andrew Z.; Sebastian, Luke; Zhao, Jean J.; Dhe‐Paganon, Sirano; Che, Jianwei; Gygi, Steven P.; Arthanari, Haribabu; Chouchani, Edward T.

doi:10.1038/s41586-023-05939-3

Cited by 93 publications

(40 citation statements)

References 70 publications

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“…As an effective secretion from living probiotics, suitable lactic acid has a positive effect to regulate physiological activity through immunoregulation, antibacterial, and other properties. 36,37 As it had not affected the normal proliferation of bacteria, the proliferative clones from L. reuteri @FeTA could stably secrete lactic acid even under the condition of gentamicin (Fig. S10, ESI†).…”

Section: Resultsmentioning

confidence: 99%

Metal-phenolic self-assembly shielded probiotics in hydrogel reinforced wound healing with antibiotic treatment

Zhou

Zou

et al. 2023

Mater. Horiz.

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Section: Resultsmentioning

confidence: 99%

Metal-phenolic self-assembly shielded probiotics in hydrogel reinforced wound healing with antibiotic treatment

Zhou

Zou

et al. 2023

Mater. Horiz.

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“…22 Proper kinetochore-microtubule attachment under proper tension satisfies spindle assembly checkpoint, allowing activation of ubiquitin ligase anaphase promoting complex/cyclosome (APC/C) to promote mitotic/meiotic exit. 24 Being one of the most dynamic posttranslational modifications, SUMOylation actively dictates a spectrum of cell-cycle events and this modification is reversed by SUMO-specific enzymes (SENPs). [23][24][25][26][27] Mammals expresses six SENPs (SENP1-3 and SENP5-7), those of which dedicate to regulating cell biology in either Sumoylation-dependent or Sumoylation-independent manner.…”

Section: Lactate As a Molecular Sensormentioning

confidence: 99%

“…24 Being one of the most dynamic posttranslational modifications, SUMOylation actively dictates a spectrum of cell-cycle events and this modification is reversed by SUMO-specific enzymes (SENPs). [23][24][25][26][27] Mammals expresses six SENPs (SENP1-3 and SENP5-7), those of which dedicate to regulating cell biology in either Sumoylation-dependent or Sumoylation-independent manner. 26 Very recently, lactate is shown to form a complex with Zn 2+ in the active site of SENP1, leading to SENP1 inhibition which thereby permits E2 ubiquitin-conjugating enzyme Ube2Cmediated APC4-K772/798 Sumoylation.…”

Section: Lactate As a Molecular Sensormentioning

confidence: 99%

The emerging era of lactate: A rising star in cellular signaling and its regulatory mechanisms

Wu,

Zhang,

Khan

et al. 2023

J of Cellular Biochemistry

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Cellular metabolites are ancient molecules with pleiotropic implications in health and disease. Beyond their cognate roles, they have signaling functions as the ligands for specific receptors and the precursors for epigenetic or posttranslational modifications. Lactate has long been recognized as a metabolic waste and fatigue product mainly produced from glycolytic metabolism. Recent evidence however suggests lactate is an unique molecule with diverse signaling attributes in orchestration of numerous biological processes, including tumor immunity and neuronal survival. The copious metabolic and non‐metabolic functions of lactate mediated by its bidirectional shuttle between cells or intracellular organelles lead to a phenotype called “lactormone.” Importantly, the mechanisms of lactate signaling, via acting as a molecular sensor and a regulator of NAD+ metabolism and AMP‐activated protein kinase signaling, and via the newly identified lactate‐driven lactylation, have been discovered. Further, we include a brief discussion about the autocrine regulation of efferocytosis by lactate in Sertoli cells which favoraerobic glycolysis. By emphasizing a repertoire of the most recent discovered mechanisms of lactate signaling, this review will open tantalizing avenues for future investigations cracking the regulatory topology of lactate signaling covered in the veil of mystery.

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“…As well, Verma and colleagues have also recently demonstrated that tumor-derived lactate can elicit epigenomic reprograming in cancer-associated fibroblasts from pancreatic ductal adenocarcinoma (Bhagat, Von Ahrens et al 2019). Moreover, W. Liu and colleagues have recently demonstrated that lactate regulates cell cycle by remodeling the anaphase promoting complex (Liu, Wang et al 2023).…”

Section: Introductionmentioning

confidence: 99%

Role of Lactate in the Regulation of Transcriptional Activity of Breast Cancer-Related Genes and Epithelial-to-Mesenchymal Transition Proteins: A Compassion of MCF7 and MDA-MB-231 Cancer Cell Lines

San-Millán

Martinez

Pickard

et al. 2023

Preprint

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The Warburg Effect is characterized by accelerated glycolytic metabolism and lactate production and is a hallmark of cancer cells. Recently, we have demonstrated the role of endogenous, glucose-derived lactate as an oncometabolite which regulates gene expression in the estrogen receptor positive (ER+) MCF7 cell line cultivated in glucose media (San-Millan, Julian et al. 2019). Presently, with the addition of a triple negative breast cancer (TNBC) cell line, MDA-MB-231, we further confirm the effect of lactate on gene expression patterns, but extend results to include lactate effects on protein expression. As well, we report effects of lactate on the expression of E-cadherin and vimentin, proteins associated with epithelial-to-mesenchymal transition (EMT). Endogenous lactate regulates the expression of multiple genes involved in carcinogenesis. In MCF7 cells, lactate increased the expression of EGFR, VEGF HIF-1a, KRAS, MIF, mTOR, PIK3CA, TP53, and CDK4 (The Ital is used for genes) as well as decreased the expression of ATM, BRCA1, BRCA2, E2F1, MET, MYC, and RAF mainly at 48h of exposure. On the other hand, in the MDA-MB-231 cell line, lactate increased the expression of PIK3CA, VEGF, EGFR, mTOR, HIF-1α, ATM, E2F1, TP53 and decreased the expression of BRCA1, BRCA2, CDK4, CDK6, MET, MIF, MYC, and RAF after 48h of exposure. Protein expression of representative genes corroborated mRNA expressions. Finally, lactate decreased E-cadherin protein expression in MCF7 cells and increased vimentin expression in MDA-MB-231 cells. In this study, we demonstrate that endogenous lactate produced under aerobic conditions (Warburg Effect) is capable of eliciting important regulation of gene and protein expression in both ER+ and TNBC cell lines. The regulation of multiple genes by lactate is widespread and involves those involved in carcinogenesis including DNA repair, cell growth, proliferation, angiogenesis, and metastasis. Furthermore, both cell lines demonstrated changes in the expression of EMT biomarkers representing a shift to a more mesenchymal phenotype with exposure to endogenous lactate.

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Lactate regulates cell cycle by remodelling the anaphase promoting complex

Cited by 93 publications

References 70 publications

Metal-phenolic self-assembly shielded probiotics in hydrogel reinforced wound healing with antibiotic treatment

Metal-phenolic self-assembly shielded probiotics in hydrogel reinforced wound healing with antibiotic treatment

The emerging era of lactate: A rising star in cellular signaling and its regulatory mechanisms

Role of Lactate in the Regulation of Transcriptional Activity of Breast Cancer-Related Genes and Epithelial-to-Mesenchymal Transition Proteins: A Compassion of MCF7 and MDA-MB-231 Cancer Cell Lines

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