» Articles » PMID: 30995715

LKB1 and Tumor Metabolism: The Interplay of Immune and Angiogenic Microenvironment in Lung Cancer

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2019 Apr 19
PMID 30995715
Citations 27
Authors
Affiliations
Soon will be listed here.
Abstract

Liver kinase B1 () is a tumor suppressor gene whose inactivation is frequent in different tumor types, especially in lung adenocarcinoma (about 30% of cases). LKB1 has an essential role in the control of cellular redox homeostasis by regulating ROS production and detoxification. Loss of LKB1 makes the tumor cell more sensitive to oxidative stress and consequently to stress-inducing treatments, such as chemotherapy and radiotherapy. LKB1 loss triggers complex changes in tumor microenvironment, supporting a role in the regulation of angiogenesis and suggesting a potential role in the response to anti-angiogenic treatment. On the other hand, LKB1 deficiency can promote an immunosuppressive microenvironment and may be involved in primary resistance to anti-PD-1/anti-PD-L1, as it has been reported in lung cancer. The aim of this review is to discuss interactions of LKB1 with the tumor microenvironment and the potential applications of this knowledge in predicting response to treatment in lung cancer.

Citing Articles

Molecular mechanism of genetic, epigenetic, and metabolic alteration in lung cancer.

Fatima S, Kumar V, Kumar D Med Oncol. 2025; 42(3):61.

PMID: 39893601 DOI: 10.1007/s12032-025-02608-5.


FBXL19 Targeted STK11 Degradation Enhances Cigarette Smoke-Induced Airway Epithelial Cell Cytotoxicity.

Li X, Lakshmi S, Uemasu K, Lane Z, Reddy R, Chandra D COPD. 2024; 21(1):2342797.

PMID: 38712759 PMC: 11186665. DOI: 10.1080/15412555.2024.2342797.


Inhibition of ERO1a and IDO1 improves dendritic cell infiltration into pancreatic ductal adenocarcinoma.

Tay A, Cinotti R, Sze N, Lundqvist A Front Immunol. 2024; 14:1264012.

PMID: 38187398 PMC: 10766682. DOI: 10.3389/fimmu.2023.1264012.


Efficacy and safety of EGFR-TKIs in combination with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant non-small-cell lung cancer: a systematic review and meta-analysis.

Hu D, Zhou Y, Ma H, Tao M, Huang Q, Yang Z BMC Pulm Med. 2023; 23(1):207.

PMID: 37316870 PMC: 10268338. DOI: 10.1186/s12890-023-02472-x.


Clinicopathological and prognostic significance of LKB1 expression in gastric cancer: a systematic review and meta-analysis.

Tan G, Liu B Sci Rep. 2023; 13(1):8937.

PMID: 37264076 PMC: 10235053. DOI: 10.1038/s41598-023-36239-5.


References
1.
Guldberg P, Thor Straten P, Ahrenkiel V, Seremet T, Kirkin A, Zeuthen J . Somatic mutation of the Peutz-Jeghers syndrome gene, LKB1/STK11, in malignant melanoma. Oncogene. 1999; 18(9):1777-80. DOI: 10.1038/sj.onc.1202486. View

2.
Hemminki A . The molecular basis and clinical aspects of Peutz-Jeghers syndrome. Cell Mol Life Sci. 1999; 55(5):735-50. PMC: 11146769. DOI: 10.1007/s000180050329. View

3.
El-Mir M, Nogueira V, Fontaine E, Averet N, Rigoulet M, Leverve X . Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem. 2000; 275(1):223-8. DOI: 10.1074/jbc.275.1.223. View

4.
Miao H, Klagsbrun M . Neuropilin is a mediator of angiogenesis. Cancer Metastasis Rev. 2001; 19(1-2):29-37. DOI: 10.1023/a:1026579711033. View

5.
Kawaguchi T, Osatomi K, Yamashita H, Kabashima T, Uyeda K . Mechanism for fatty acid "sparing" effect on glucose-induced transcription: regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase. J Biol Chem. 2001; 277(6):3829-35. DOI: 10.1074/jbc.M107895200. View