Tumor Promoting Function of DUSP10 in Non-Small Cell Lung Cancer Is Associated With Tumor-Promoting Cytokines
3
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.
Abstract
Lung cancer, particularly non-small cell lung cancer (NSCLC) which contributes more than 80% to totally lung cancer cases, remains the leading cause of cancer death and the 5-year survival is less than 20%. Continuous understanding on the mechanisms underlying the pathogenesis of this disease and identification of biomarkers for therapeutic application and response to treatment will help to improve patient survival. Here we found that a molecule known as DUSP10 (also known as MAPK phosphatase 5) is oncogenic in NSCLC. Overexpression of DUSP10 in NSCLC cells resulted in reduced activation of ERK and JNK, but increased activation of p38, which was associated with increased cellular growth and migration. When inoculated in immunodeficient mice, the DUSP10-overexpression NSCLC cells formed larger tumors compared to control cells. The increased growth of DUSP10-overexpression NSCLC cells was associated with increased expression of tumor-promoting cytokines including IL-6 and TGFβ. Importantly, higher DUSP10 expression was associated with poorer prognosis of NSCLC patients. Therefore, DUSP10 could severe as a biomarker for NSCLC prognosis and could be a target for development of therapeutic method for lung cancer treatment.
참고문헌 (26)
- Bade BC, "Lung cancer 2020 : epidemiology, etiology, and prevention", Clin Chest Med, 41, pp.1~24 (2020)
- Nooreldeen R, "Current and future development in lung cancer diagnosis", Int J Mol Sci, 22, pp.8661~ (2021)
- Kozaki K, "Establishment and characterization of a human lung cancer cell line NCI-H460-LNM35 with consistent lymphogenous metastasis via both subcutaneous and orthotopic propagation", Cancer Res, 60, pp.2535~2540 (2000)
- Takahashi M, "Activating mutations in EGFR and PI3K promote ATF4 induction for NSCLC cell survival during amino acid deprivation", Heliyon(Lond), 9, pp.e14799~ (2023)
- da Cunha Santos G, "EGFR mutations and lung cancer", Annu Rev Pathol, 6, pp.49~69 (2011)
- Prior IA, "A comprehensive survey of Ras mutations in cancer", Cancer Res, 72, pp.2457~2467 (2012)
- Dankner M, "Classifying BRAF alterations in cancer : new rational therapeutic strategies for actionable mutations", Oncogene, 37, pp.3183~3199 (2018)
- Lavoie H, "ERK signalling : a master regulator of cell behaviour, life and fate", Nat Rev Mol Cell Biol, 21, pp.607~632 (2020)
- Caunt CJ, "Dual-specificity MAP kinase phosphatases(MKPs) : shaping the outcome of MAP kinase signalling", FEBS J, 280, pp.489~504 (2013)
- Heng Boon Low, "Regulatory Roles of MAPK Phosphatases in Cancer", Immune Network, 16(2), pp.85~98 (2016), 대한면역학회[DOI]
- Png CW, "DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis", Oncogene, 35, pp.206~217 (2016)
- Low HB, "DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death", Nat Commun, 12, pp.2284~ (2021)
- Fukuyama T, "Cytokine production of lung cancer cell lines : correlation between their production and the inflammatory", immunological responses both in vivo and in vitro, 2007, pp.98, 1048~1054
- Zhang Y, "Regulation of innate and adaptive immune responses by MAP kinase phosphatase 5", Nature, 430, pp.793~797 (2004)
- An J, "Serum IL-6 as a vital predictor of severe lung cancer", Ann Palliat Med, 10, pp.202~209 (2021)
- Liu C, "Systematic analysis of IL-6 as a predictive biomarker and desensitizer of immunotherapy responses in patients with non-small cell lung cancer", BMC Med, 20, pp.187~ (2022)
- Tong X, "MYOCD and SMAD3", SMAD4 form a positive feedback loop and drive TGF-β-induced epithelial-mesenchymal transition in non-small cell lung cancer, 2020, pp.39, 2890~2904
- Li J, "Prognostic value of TGF-β in lung cancer : systematic review and meta-analysis", BMC Cancer, 19, pp.691~ (2019)
- Zappa C, "Non-small cell lung cancer : current treatment and future advances", Transl Lung Cancer Res, 5, pp.288~300 (2016)
- Komnenovic V, "p38α suppresses normal and cancer cell proliferation by antagonizing the JNK–c-Jun pathway", Nat Genet, 39, pp.741~749 (2007)
- Dolado I, "p38α MAP kinase as a sensor of reactive oxygen species in tumorigenesis", Cancer Cell, 11, pp.191~205 (2007)
- Cánovas B, "Targeting p38α increases DNA damage, chromosome instability, and the anti-tumoral response to taxanes in breast cancer cells", Cancer Cell, 33, pp.1094~1110 (2018)
- Greenberg AK, "Selective p38 activation in human non-small cell lung cancer", Am J Respir Cell Mol Biol, 26, pp.558~564 (2002)
- Liu H, "HOXC8 promotes proliferation and migration through transcriptional up-regulation of TGFβ1 in non-small cell lung cancer", Oncogenesis, 7, pp.1~ (2018)
- Liu SG, "The clinical research of serum VEGF, TGF-β1, and endostatin in non-small cell lung cancer", Cell Biochem Biophys, 72, pp.165~169 (2015)
- Zhang YE, "Non-Smad pathways in TGF-beta signaling", Cell Res, 19, pp.128~139 (2009)