Regulation of glycolysis and cancer cell proliferation by PKM2 citrullination

Coassolo, Sébastien; Davidson, Irwin

doi:10.1080/23723556.2021.1927446

Cited by 3 publications

(4 citation statements)

References 10 publications

(7 reference statements)

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“…PADIs are highly expressed in a wide range of human malignant cancers, together with the fact that synthetic PADI inhibitors can lead to apoptosis and changes in mitochondrial structure in cancer cells; this strongly suggests that PADIs play important roles in tumorigenesis [ 30 , 31 ]. PADI3 seems to be cell-type dependent and is mostly expressed in solid tumors, such as those associated with bladder, pancreatic, cervical, head and neck, and clear-cell renal cancers, which are known to possess a hypoxic character [ 17 ], while it is weakly expressed in colon cancer, acting as a tumor suppressor gene [ 32 , 33 ]. In multiple cancer cell types, PADI3 modulates PKM2 citrulline to contribute to increased glycolysis and cell proliferation [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Peptidyl arginine deiminase 3 (PADI3) belongs to the peptidyl arginine deiminase family and is a post-translational protein modification enzyme that can catalyze the conversion of arginine to citrulline, and this progress is known as citrullination. It has been reported that PADI3 is highly expressed in some solid tumors, such as bladder, pancreatic, cervical, head and neck, and clear-cell renal cancers, in which increased PADI3 enhances the citrullination of the glycolytic rate-limiting enzyme PKM2, leading to increased levels of glycolysis [ 17 , 18 ]. Nevertheless, the roles of PADI3 in endometrial cancer have not been previously explored.…”

Section: Introductionmentioning

confidence: 99%

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Atractylenolide II Suppresses Glycolysis and Induces Apoptosis by Blocking the PADI3-ERK Signaling Pathway in Endometrial Cancer Cells

Tian,

Ren,

Liu

et al. 2024

Molecules

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Atractylenolide II (AT-II), the major bioactive compound of Atractylodes macrocephala, exhibits anti-cancer activity against many types of tumors, but the roles and the potential mechanisms in endometrial cancer remain unclear. In the present study, AT-II treatment was found to significantly suppress RL95-2 and AN3CA cell proliferation and glycolysis, and induced their apoptosis by inactivating the ERK signaling pathway, accompanied by the changing expression of the glycolytic key enzymes and apoptotic-related proteins. Peptidyl arginine deiminase 3 (PADI3), as the candidate target gene of AT-II, was highly expressed in the endometrial cancer tissues and associated with a poor prognosis according to bioinformatics analysis. PADI3 knockdown inhibited proliferation and glycolysis in endometrial cancer cells and induced cell apoptosis. Furthermore, AT-II negatively regulated the expression of PADI3, and PADI3 overexpression reversed the effects of AT-II on endometrial cancer cells. Our findings suggested that the anti-cancer function of AT-II is associated with the suppression of glycolysis and induction of apoptosis by blocking the PADI3-ERK signaling pathway. Thus, AT-II represents a novel therapeutic target for endometrial cancer and targeting AT-II may serve as a potential strategy for the clinical therapy of endometrial cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Atractylenolide II Suppresses Glycolysis and Induces Apoptosis by Blocking the PADI3-ERK Signaling Pathway in Endometrial Cancer Cells

Tian,

Ren,

Liu

et al. 2024

Molecules

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“…Studies have shown that the PADI family can participate in energy metabolism. PADI1 and PADI3 can promote glycolysis through citrulline pyruvate kinase M2 (PKM2) arginine 106, leading to the proliferation of cancer cells ( 77 , 78 ). In addition, TINCR promotes de novo lipid biosynthesis and histone H3K27 acetylation by preventing the ubiquitination and degradation of ACLY, leading to the accumulation of acetyl-CoA in cells.…”

Section: Physiological Processes Involving the Padi Familymentioning

confidence: 99%

“…First, PADI1 can affect the proliferation of tumor cells by participating in energy metabolism. The citrullination of Arg 10 in PKM2 by PADI1 can lead to an increase in glycolysis, thus promoting the proliferation of cancer cells ( 77 , 78 ). Second, PADI1 can promote EMT and metastasis of triple-negative breast cancer cells by regulating MEK1-ERK1/2-MMP2 signal transduction ( 143 ).…”

Section: The Padi Family and Cancermentioning

confidence: 99%

Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review

2023

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The peptidyl arginine deiminase (PADI) family is a calcium ion-dependent group of isozymes with sequence similarity that catalyze the citrullination of proteins. Histones can serve as the target substrate of PADI family isozymes, and therefore, the PADI family is involved in NETosis and the secretion of inflammatory cytokines. Thus, the PADI family is associated with the development of inflammatory autoimmune diseases and cancer, reproductive development, and other related diseases. In this review, we systematically discuss the role of the PADI family in the pathogenesis of various diseases based on studies from the past decade to provide a reference for future research.

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Peptidylarginine deiminase enzymes and citrullinated proteins in female reproductive physiology and associated diseases

Christensen

Young

et al. 2022

Biology of Reproduction

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Citrullination, the post-translational modification of arginine residues, is catalyzed by the four catalytically active peptidylarginine deiminase (PAD or PADI) isozymes and alters charge to affect target protein structure and function. PADs were initially characterized in rodent uteri, and since then, have been described in other female tissues including ovaries, breast, and the lactotrope and gonadotrope cells of the anterior pituitary gland. In these tissues and cells, estrogen robustly stimulates PAD expression resulting in changes in levels over the course of the female reproductive cycle. The best characterized targets for PADs are arginine residues in histone tails, which, when citrullinated, alter chromatin structure and gene expression. Methodological advances have allowed for the identification of tissue-specific citrullinomes, which reveal that PADs citrullinate a wide range of enzymes and structural proteins to alter cell function. In contrast to their important physiological roles, PADs and citrullinated proteins are also involved in several female specific diseases including autoimmune disorders and reproductive cancers. Herein, we review current knowledge regarding PAD expression and function and highlight the role of protein citrullination in both normal female reproductive tissues and associated diseases.

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Regulation of glycolysis and cancer cell proliferation by PKM2 citrullination

Cited by 3 publications

References 10 publications

Atractylenolide II Suppresses Glycolysis and Induces Apoptosis by Blocking the PADI3-ERK Signaling Pathway in Endometrial Cancer Cells

Atractylenolide II Suppresses Glycolysis and Induces Apoptosis by Blocking the PADI3-ERK Signaling Pathway in Endometrial Cancer Cells

Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review

Peptidylarginine deiminase enzymes and citrullinated proteins in female reproductive physiology and associated diseases

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