TIPE Drives a Cancer Stem-like Phenotype by Promoting Glycolysis Via PKM2/HIF-1α Axis in Melanoma

Overview

Journal Elife

Specialty Biology

Date 2024 Dec 27

PMID 39728923

Authors

Maojin Tian

Le Yang

Ziqian Zhao

Jigang Li

Lianqing Wang

Qingqing Yin

Wei Hu

Yunwei Lou

Jianxin Du

Peiqing Zhao

Affiliations

Soon will be listed here.

Abstract

TIPE () has been identified as an oncogene and participates in tumor biology. However, how its role in the metabolism of tumor cells during melanoma development remains unclear. Here, we demonstrated that TIPE promoted glycolysis by interacting with pyruvate kinase M2 (PKM2) in melanoma. We found that TIPE-induced PKM2 dimerization, thereby facilitating its translocation from the cytoplasm to the nucleus. TIPE-mediated PKM2 dimerization consequently promoted HIF-1α activation and glycolysis, which contributed to melanoma progression and increased its stemness features. Notably, TIPE specifically phosphorylated PKM2 at Ser 37 in an extracellular signal-regulated kinase (ERK)-dependent manner. Consistently, the expression of TIPE was positively correlated with the levels of PKM2 Ser37 phosphorylation and cancer stem cell (CSC) markers in melanoma tissues from clinical samples and tumor bearing mice. In summary, our findings indicate that the TIPE/PKM2/HIF-1α signaling pathway plays a pivotal role in promoting CSC properties by facilitating the glycolysis, which would provide a promising therapeutic target for melanoma intervention.

Citing Articles

TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma.

Tian M, Yang L, Zhao Z, Li J, Wang L, Yin Q Elife. 2024; 13.

PMID: 39728923 PMC: 11677236. DOI: 10.7554/eLife.92741.

References

Hu Y, Smyth G . ELDA: extreme limiting dilution analysis for comparing depleted and enriched populations in stem cell and other assays. J Immunol Methods. 2009; 347(1-2):70-8. DOI: 10.1016/j.jim.2009.06.008. View

Morgan H, OReilly F, Wear M, ONeill J, Fothergill-Gilmore L, Hupp T . M2 pyruvate kinase provides a mechanism for nutrient sensing and regulation of cell proliferation. Proc Natl Acad Sci U S A. 2013; 110(15):5881-6. PMC: 3625322. DOI: 10.1073/pnas.1217157110. View

Icard P, Simula L, Fournel L, Leroy K, Lupo A, Damotte D . The strategic roles of four enzymes in the interconnection between metabolism and oncogene activation in non-small cell lung cancer: Therapeutic implications. Drug Resist Updat. 2022; 63:100852. DOI: 10.1016/j.drup.2022.100852. View

Faubert B, Solmonson A, DeBerardinis R . Metabolic reprogramming and cancer progression. Science. 2020; 368(6487). PMC: 7227780. DOI: 10.1126/science.aaw5473. View

Cui C, Chak-Lui Wong C, Kai A, Ho D, Lau E, Tsui Y . SENP1 promotes hypoxia-induced cancer stemness by HIF-1α deSUMOylation and SENP1/HIF-1α positive feedback loop. Gut. 2017; 66(12):2149-2159. PMC: 5749365. DOI: 10.1136/gutjnl-2016-313264. View

Dhanesha N, Patel R, Doddapattar P, Ghatge M, Flora G, Jain M . PKM2 promotes neutrophil activation and cerebral thromboinflammation: therapeutic implications for ischemic stroke. Blood. 2021; 139(8):1234-1245. PMC: 8874361. DOI: 10.1182/blood.2021012322. View

Yang W, Zheng Y, Xia Y, Ji H, Chen X, Guo F . ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat Cell Biol. 2012; 14(12):1295-304. PMC: 3511602. DOI: 10.1038/ncb2629. View

Zhou Q, Yin Y, Yu M, Gao D, Sun J, Yang Z . GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism. Redox Biol. 2022; 56:102458. PMC: 9483790. DOI: 10.1016/j.redox.2022.102458. View

Yang Y, Chien M, Liu H, Chang Y, Chen C, Lee W . Nuclear translocation of PKM2/AMPK complex sustains cancer stem cell populations under glucose restriction stress. Cancer Lett. 2018; 421:28-40. DOI: 10.1016/j.canlet.2018.01.075. View

10.

Puckett D, AlQuraishi M, Chowanadisai W, Bettaieb A . The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs. Int J Mol Sci. 2021; 22(3). PMC: 7865720. DOI: 10.3390/ijms22031171. View

11.

Li N, Feng L, Liu H, Wang J, Kasembeli M, Tran M . PARP Inhibition Suppresses Growth of EGFR-Mutant Cancers by Targeting Nuclear PKM2. Cell Rep. 2016; 15(4):843-856. PMC: 5063668. DOI: 10.1016/j.celrep.2016.03.070. View

12.

Chen C, Zhang W, Zhou T, Liu Q, Han C, Huang Z . Vitamin B5 rewires Th17 cell metabolism via impeding PKM2 nuclear translocation. Cell Rep. 2022; 41(9):111741. DOI: 10.1016/j.celrep.2022.111741. View

13.

Guo D, Tong Y, Jiang X, Meng Y, Jiang H, Du L . Aerobic glycolysis promotes tumor immune evasion by hexokinase2-mediated phosphorylation of IκBα. Cell Metab. 2022; 34(9):1312-1324.e6. DOI: 10.1016/j.cmet.2022.08.002. View

14.

Zhu B, Zhong W, Cao X, Pan G, Xu M, Zheng J . Loss of miR-31-5p drives hematopoietic stem cell malignant transformation and restoration eliminates leukemia stem cells in mice. Sci Transl Med. 2022; 14(629):eabh2548. DOI: 10.1126/scitranslmed.abh2548. View

15.

Ouyang X, Han S, Zhang J, Dioletis E, Nemeth B, Pacher P . Digoxin Suppresses Pyruvate Kinase M2-Promoted HIF-1α Transactivation in Steatohepatitis. Cell Metab. 2018; 27(2):339-350.e3. PMC: 5806149. DOI: 10.1016/j.cmet.2018.01.007. View

16.

Yang M, Zhang Y, Liu G, Zhao Z, Li J, Yang L . TIPE1 inhibits osteosarcoma tumorigenesis and progression by regulating PRMT1 mediated STAT3 arginine methylation. Cell Death Dis. 2022; 13(9):815. PMC: 9508122. DOI: 10.1038/s41419-022-05273-y. View

17.

Novoyatleva T, Rai N, Weissmann N, Grimminger F, Ghofrani H, Seeger W . Is PKM2 Phosphorylation a Prerequisite for Oligomer Disassembly in Pulmonary Arterial Hypertension?. Am J Respir Crit Care Med. 2019; 200(12):1550-1554. DOI: 10.1164/rccm.201904-0782LE. View

18.

Zhang Z, Deng X, Liu Y, Liu Y, Sun L, Chen F . PKM2, function and expression and regulation. Cell Biosci. 2019; 9:52. PMC: 6595688. DOI: 10.1186/s13578-019-0317-8. View

19.

Zhao P, Pang X, Jiang J, Wang L, Zhu X, Yin Y . TIPE1 promotes cervical cancer progression by repression of p53 acetylation and is associated with poor cervical cancer outcome. Carcinogenesis. 2018; 40(4):592-599. DOI: 10.1093/carcin/bgy163. View

20.

Cluntun A, Lukey M, Cerione R, Locasale J . Glutamine Metabolism in Cancer: Understanding the Heterogeneity. Trends Cancer. 2017; 3(3):169-180. PMC: 5383348. DOI: 10.1016/j.trecan.2017.01.005. View