TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma
TIPE (TNFAIP8) 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 f...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/92741 |
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| author | Maojin Tian Le Yang Ziqian Zhao Jigang Li Lianqing Wang Qingqing Yin Wei Hu Yunwei Lou Jianxin Du Peiqing Zhao |
| author_facet | Maojin Tian Le Yang Ziqian Zhao Jigang Li Lianqing Wang Qingqing Yin Wei Hu Yunwei Lou Jianxin Du Peiqing Zhao |
| author_sort | Maojin Tian |
| collection | DOAJ |
| description | TIPE (TNFAIP8) 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. |
| format | Article |
| id | doaj-art-cecddf8e57b14d8daaf6007d87b77c80 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-cecddf8e57b14d8daaf6007d87b77c802025-08-20T02:55:39ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011310.7554/eLife.92741TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanomaMaojin Tian0https://orcid.org/0009-0004-9302-0162Le Yang1Ziqian Zhao2Jigang Li3Lianqing Wang4Qingqing Yin5Wei Hu6Yunwei Lou7Jianxin Du8Peiqing Zhao9https://orcid.org/0000-0002-9311-1927Center of Translational Medicine, Zibo Central Hospital Affiliated to Binzhou Medical University, Zibo, ChinaShandong First Medical University, Jinan, ChinaThe Second Medical College, Xinjiang Medical University, Urumqi, ChinaCenter of Translational Medicine, Zibo Central Hospital Affiliated to Binzhou Medical University, Zibo, ChinaCenter of Translational Medicine, Zibo Central Hospital Affiliated to Binzhou Medical University, Zibo, ChinaShandong First Medical University, Jinan, ChinaCenter of Translational Medicine, Zibo Central Hospital Affiliated to Binzhou Medical University, Zibo, ChinaSchool of Laboratory Medicine, Xinxiang Medical University, Xinxiang, ChinaCenter of Translational Medicine, Zibo Central Hospital Affiliated to Binzhou Medical University, Zibo, ChinaCenter of Translational Medicine, Zibo Central Hospital Affiliated to Binzhou Medical University, Zibo, ChinaTIPE (TNFAIP8) 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.https://elifesciences.org/articles/92741TIPEglycolysisPKM2HIF-1αmelanoma |
| spellingShingle | Maojin Tian Le Yang Ziqian Zhao Jigang Li Lianqing Wang Qingqing Yin Wei Hu Yunwei Lou Jianxin Du Peiqing Zhao TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma eLife TIPE glycolysis PKM2 HIF-1α melanoma |
| title | TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma |
| title_full | TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma |
| title_fullStr | TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma |
| title_full_unstemmed | TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma |
| title_short | TIPE drives a cancer stem-like phenotype by promoting glycolysis via PKM2/HIF-1α axis in melanoma |
| title_sort | tipe drives a cancer stem like phenotype by promoting glycolysis via pkm2 hif 1α axis in melanoma |
| topic | TIPE glycolysis PKM2 HIF-1α melanoma |
| url | https://elifesciences.org/articles/92741 |
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