Lactate Dehydrogenase B Is Required for Pancreatic Cancer Cell Immortalization Through Activation of Telomerase Activity
Telomerase activity is elevated in most cancer cells and is required for telomere length maintenance and immortalization of cancer cells. Glucose metabolic reprogramming is a hallmark of cancer and accompanied with increased expression of key metabolic enzymes. Whether these enzymes influence telome...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.821620/full |
| _version_ | 1818215605775368192 |
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| author | Ruiguan Wang Ruiguan Wang Ruiguan Wang Jiangbo Li Changjian Zhang Changjian Zhang Xin Guan Boyu Qin Rui Jin Lingmei Qin Shanrong Xu Shanrong Xu Xiaona Zhang Xiaona Zhang Rong Liu Rong Liu Qinong Ye Long Cheng |
| author_facet | Ruiguan Wang Ruiguan Wang Ruiguan Wang Jiangbo Li Changjian Zhang Changjian Zhang Xin Guan Boyu Qin Rui Jin Lingmei Qin Shanrong Xu Shanrong Xu Xiaona Zhang Xiaona Zhang Rong Liu Rong Liu Qinong Ye Long Cheng |
| author_sort | Ruiguan Wang |
| collection | DOAJ |
| description | Telomerase activity is elevated in most cancer cells and is required for telomere length maintenance and immortalization of cancer cells. Glucose metabolic reprogramming is a hallmark of cancer and accompanied with increased expression of key metabolic enzymes. Whether these enzymes influence telomerase activity and cell immortalization remains unclear. In the current study, we screened metabolic enzymes using telomerase activity assay and identified lactate dehydrogenase B (LDHB) as a regulator of telomerase activity. Sodium lactate and sodium pyruvate did not influence telomerase activity, indicating LDHB regulates telomerase activity independent of its metabolism regulating function. Further studies revealed that LDHB directly interacted with TERT and regulated the interaction between TERT and TERC. Additionally, long-term knockdown of LDHB inhibited cancer cell growth and induced cell senescence in vitro and in vivo. Higher LDHB expression was detected in pancreatic cancer tissues compared with that in adjacent normal tissues and expression of LDHB correlated negatively with prognosis. Thus, we identified LDHB as the first glucose metabolic enzyme contributing to telomerase activity and pancreatic cancer cell immortalization. |
| first_indexed | 2024-12-12T06:38:44Z |
| format | Article |
| id | doaj.art-3ec60f619f154321911c764c53ba2c0f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T06:38:44Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3ec60f619f154321911c764c53ba2c0f2022-12-22T00:34:25ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-05-011210.3389/fonc.2022.821620821620Lactate Dehydrogenase B Is Required for Pancreatic Cancer Cell Immortalization Through Activation of Telomerase ActivityRuiguan Wang0Ruiguan Wang1Ruiguan Wang2Jiangbo Li3Changjian Zhang4Changjian Zhang5Xin Guan6Boyu Qin7Rui Jin8Lingmei Qin9Shanrong Xu10Shanrong Xu11Xiaona Zhang12Xiaona Zhang13Rong Liu14Rong Liu15Qinong Ye16Long Cheng17Department of Cell Engineering, Beijing Institute of Biotechnology, Beijing, ChinaFaculty of Hepato-Pancreato-Biliary Surgery, Chinese People's Liberation Army (PLA) General Hospital, Beijing, ChinaDepartment of Hepatobiliary Surgery, the Eight Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, ChinaDepartment of Cell Engineering, Beijing Institute of Biotechnology, Beijing, ChinaDepartment of Cell Engineering, Beijing Institute of Biotechnology, Beijing, ChinaSenior Department of Otolaryngology-Head & Neck Surgery, the Sixth Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, ChinaStrategic Support Force Medical Center, Beijing, ChinaDepartment of Medical Oncology, the First Medical Centre, Chinese People's Liberation Army (PLA) General Hospital, Beijing, ChinaDepartment of Cell Engineering, Beijing Institute of Biotechnology, Beijing, ChinaDepartment of Cell Engineering, Beijing Institute of Biotechnology, Beijing, ChinaDepartment of Cell Engineering, Beijing Institute of Biotechnology, Beijing, ChinaSchool of Life Science, Anqing Normal University, Anqing, ChinaDepartment of Cell Engineering, Beijing Institute of Biotechnology, Beijing, ChinaCollege of Life Sciences, Capital Normal University, Beijing, ChinaFaculty of Hepato-Pancreato-Biliary Surgery, Chinese People's Liberation Army (PLA) General Hospital, Beijing, ChinaDepartment of Hepatobiliary Surgery, the Eight Medical Center, Chinese People's Liberation Army (PLA) General Hospital, Beijing, ChinaDepartment of Cell Engineering, Beijing Institute of Biotechnology, Beijing, ChinaDepartment of Cell Engineering, Beijing Institute of Biotechnology, Beijing, ChinaTelomerase activity is elevated in most cancer cells and is required for telomere length maintenance and immortalization of cancer cells. Glucose metabolic reprogramming is a hallmark of cancer and accompanied with increased expression of key metabolic enzymes. Whether these enzymes influence telomerase activity and cell immortalization remains unclear. In the current study, we screened metabolic enzymes using telomerase activity assay and identified lactate dehydrogenase B (LDHB) as a regulator of telomerase activity. Sodium lactate and sodium pyruvate did not influence telomerase activity, indicating LDHB regulates telomerase activity independent of its metabolism regulating function. Further studies revealed that LDHB directly interacted with TERT and regulated the interaction between TERT and TERC. Additionally, long-term knockdown of LDHB inhibited cancer cell growth and induced cell senescence in vitro and in vivo. Higher LDHB expression was detected in pancreatic cancer tissues compared with that in adjacent normal tissues and expression of LDHB correlated negatively with prognosis. Thus, we identified LDHB as the first glucose metabolic enzyme contributing to telomerase activity and pancreatic cancer cell immortalization.https://www.frontiersin.org/articles/10.3389/fonc.2022.821620/fullLDHBtelomerasetelomerepancreatic cancercell senescence |
| spellingShingle | Ruiguan Wang Ruiguan Wang Ruiguan Wang Jiangbo Li Changjian Zhang Changjian Zhang Xin Guan Boyu Qin Rui Jin Lingmei Qin Shanrong Xu Shanrong Xu Xiaona Zhang Xiaona Zhang Rong Liu Rong Liu Qinong Ye Long Cheng Lactate Dehydrogenase B Is Required for Pancreatic Cancer Cell Immortalization Through Activation of Telomerase Activity Frontiers in Oncology LDHB telomerase telomere pancreatic cancer cell senescence |
| title | Lactate Dehydrogenase B Is Required for Pancreatic Cancer Cell Immortalization Through Activation of Telomerase Activity |
| title_full | Lactate Dehydrogenase B Is Required for Pancreatic Cancer Cell Immortalization Through Activation of Telomerase Activity |
| title_fullStr | Lactate Dehydrogenase B Is Required for Pancreatic Cancer Cell Immortalization Through Activation of Telomerase Activity |
| title_full_unstemmed | Lactate Dehydrogenase B Is Required for Pancreatic Cancer Cell Immortalization Through Activation of Telomerase Activity |
| title_short | Lactate Dehydrogenase B Is Required for Pancreatic Cancer Cell Immortalization Through Activation of Telomerase Activity |
| title_sort | lactate dehydrogenase b is required for pancreatic cancer cell immortalization through activation of telomerase activity |
| topic | LDHB telomerase telomere pancreatic cancer cell senescence |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.821620/full |
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