KLF8 Promotes the Survival of Lung Adenocarcinoma During Nutrient Deprivation by Regulating the Pentose Phosphate Pathway through SIRT2
Background: The pentose phosphate pathway (PPP) is a critical metabolic pathway that generates NADPH and ribose-5-phosphate for nucleotide biosynthesis and redox homeostasis. In this study, we investigated a potential regulatory role for Krüppel-like factor 8 (KLF8) in the control of PPP in lung ade...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
IMR Press
2024-01-01
|
Series: | Frontiers in Bioscience-Landmark |
Subjects: | |
Online Access: | https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901027 |
_version_ | 1797338810062733312 |
---|---|
author | Qiaohong Bai Wenfang Jin Futao Chen Jiang Zhu Lifeng Cao Yang Yang Fukuan Zhong Li Li |
author_facet | Qiaohong Bai Wenfang Jin Futao Chen Jiang Zhu Lifeng Cao Yang Yang Fukuan Zhong Li Li |
author_sort | Qiaohong Bai |
collection | DOAJ |
description | Background: The pentose phosphate pathway (PPP) is a critical metabolic pathway that generates NADPH and ribose-5-phosphate for nucleotide biosynthesis and redox homeostasis. In this study, we investigated a potential regulatory role for Krüppel-like factor 8 (KLF8) in the control of PPP in lung adenocarcinoma (LUAD) cells. Methods: Based on a comprehensive set of experimental approaches, including cell culture, molecular techniques, and functional assays, we revealed a novel mechanism by which KLF8 promotes the activation of glucose-6-phosphate dehydrogenase (G6PD), a component enzyme in the PPP. Results: Our findings demonstrate that KLF8 inhibits the acetylation of G6PD, leading to its increased enzymatic activity. Additionally, we observed that KLF8 activates the transcription of SIRT2, which has been implicated in regulating G6PD acetylation. These results highlight the interplay between KLF8, G6PD, and protein acetylation in the regulation of PPP in LUAD. Conclusions: Understanding the intricate molecular mechanisms underlying the metabolic reprogramming driven by KLF8 in lung cancer provides valuable insights into potential therapeutic strategies targeting the PPP. This study emphasizes the significance of KLF8 as a key modulator of metabolic pathways and indicates the potential of targeting the KLF8-G6PD axis for lung cancer treatment. |
first_indexed | 2024-03-08T09:36:43Z |
format | Article |
id | doaj.art-43a6cfb8206f4c428dc83d2ff28a0761 |
institution | Directory Open Access Journal |
issn | 2768-6701 |
language | English |
last_indexed | 2024-03-08T09:36:43Z |
publishDate | 2024-01-01 |
publisher | IMR Press |
record_format | Article |
series | Frontiers in Bioscience-Landmark |
spelling | doaj.art-43a6cfb8206f4c428dc83d2ff28a07612024-01-30T07:44:34ZengIMR PressFrontiers in Bioscience-Landmark2768-67012024-01-012912710.31083/j.fbl2901027S2768-6701(23)01069-9KLF8 Promotes the Survival of Lung Adenocarcinoma During Nutrient Deprivation by Regulating the Pentose Phosphate Pathway through SIRT2Qiaohong Bai0Wenfang Jin1Futao Chen2Jiang Zhu3Lifeng Cao4Yang Yang5Fukuan Zhong6Li Li7Department of Respiratory, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210000 Nanjing, Jiangsu, ChinaDepartment of Respiratory, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, 210000 Nanjing, Jiangsu, ChinaDepartment of Respiratory, The Second Hospital of Lianyungang, 222000 Lianyungang, Jiangsu, ChinaDepartment of Respiratory, The Second Hospital of Lianyungang, 222000 Lianyungang, Jiangsu, ChinaDepartment of Respiratory, The Second Hospital of Lianyungang, 222000 Lianyungang, Jiangsu, ChinaDepartment of Respiratory, The Second Hospital of Lianyungang, 222000 Lianyungang, Jiangsu, ChinaDepartment of Respiratory, The Second Hospital of Lianyungang, 222000 Lianyungang, Jiangsu, ChinaDepartment of Respiratory, Nanjing Chest Hospital, Affiliated Nanjing Brain Hospital, Nanjing Medical University, 210000 Nanjing, Jiangsu, ChinaBackground: The pentose phosphate pathway (PPP) is a critical metabolic pathway that generates NADPH and ribose-5-phosphate for nucleotide biosynthesis and redox homeostasis. In this study, we investigated a potential regulatory role for Krüppel-like factor 8 (KLF8) in the control of PPP in lung adenocarcinoma (LUAD) cells. Methods: Based on a comprehensive set of experimental approaches, including cell culture, molecular techniques, and functional assays, we revealed a novel mechanism by which KLF8 promotes the activation of glucose-6-phosphate dehydrogenase (G6PD), a component enzyme in the PPP. Results: Our findings demonstrate that KLF8 inhibits the acetylation of G6PD, leading to its increased enzymatic activity. Additionally, we observed that KLF8 activates the transcription of SIRT2, which has been implicated in regulating G6PD acetylation. These results highlight the interplay between KLF8, G6PD, and protein acetylation in the regulation of PPP in LUAD. Conclusions: Understanding the intricate molecular mechanisms underlying the metabolic reprogramming driven by KLF8 in lung cancer provides valuable insights into potential therapeutic strategies targeting the PPP. This study emphasizes the significance of KLF8 as a key modulator of metabolic pathways and indicates the potential of targeting the KLF8-G6PD axis for lung cancer treatment.https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901027pentose phosphate pathwaynutrient deprivationklf8tumor metabolism |
spellingShingle | Qiaohong Bai Wenfang Jin Futao Chen Jiang Zhu Lifeng Cao Yang Yang Fukuan Zhong Li Li KLF8 Promotes the Survival of Lung Adenocarcinoma During Nutrient Deprivation by Regulating the Pentose Phosphate Pathway through SIRT2 Frontiers in Bioscience-Landmark pentose phosphate pathway nutrient deprivation klf8 tumor metabolism |
title | KLF8 Promotes the Survival of Lung Adenocarcinoma During Nutrient Deprivation by Regulating the Pentose Phosphate Pathway through SIRT2 |
title_full | KLF8 Promotes the Survival of Lung Adenocarcinoma During Nutrient Deprivation by Regulating the Pentose Phosphate Pathway through SIRT2 |
title_fullStr | KLF8 Promotes the Survival of Lung Adenocarcinoma During Nutrient Deprivation by Regulating the Pentose Phosphate Pathway through SIRT2 |
title_full_unstemmed | KLF8 Promotes the Survival of Lung Adenocarcinoma During Nutrient Deprivation by Regulating the Pentose Phosphate Pathway through SIRT2 |
title_short | KLF8 Promotes the Survival of Lung Adenocarcinoma During Nutrient Deprivation by Regulating the Pentose Phosphate Pathway through SIRT2 |
title_sort | klf8 promotes the survival of lung adenocarcinoma during nutrient deprivation by regulating the pentose phosphate pathway through sirt2 |
topic | pentose phosphate pathway nutrient deprivation klf8 tumor metabolism |
url | https://www.imrpress.com/journal/FBL/29/1/10.31083/j.fbl2901027 |
work_keys_str_mv | AT qiaohongbai klf8promotesthesurvivaloflungadenocarcinomaduringnutrientdeprivationbyregulatingthepentosephosphatepathwaythroughsirt2 AT wenfangjin klf8promotesthesurvivaloflungadenocarcinomaduringnutrientdeprivationbyregulatingthepentosephosphatepathwaythroughsirt2 AT futaochen klf8promotesthesurvivaloflungadenocarcinomaduringnutrientdeprivationbyregulatingthepentosephosphatepathwaythroughsirt2 AT jiangzhu klf8promotesthesurvivaloflungadenocarcinomaduringnutrientdeprivationbyregulatingthepentosephosphatepathwaythroughsirt2 AT lifengcao klf8promotesthesurvivaloflungadenocarcinomaduringnutrientdeprivationbyregulatingthepentosephosphatepathwaythroughsirt2 AT yangyang klf8promotesthesurvivaloflungadenocarcinomaduringnutrientdeprivationbyregulatingthepentosephosphatepathwaythroughsirt2 AT fukuanzhong klf8promotesthesurvivaloflungadenocarcinomaduringnutrientdeprivationbyregulatingthepentosephosphatepathwaythroughsirt2 AT lili klf8promotesthesurvivaloflungadenocarcinomaduringnutrientdeprivationbyregulatingthepentosephosphatepathwaythroughsirt2 |