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...

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Main Authors: Qiaohong Bai, Wenfang Jin, Futao Chen, Jiang Zhu, Lifeng Cao, Yang Yang, Fukuan Zhong, Li Li
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
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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.
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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
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