MAP3K3 expression in tumor cells and tumor-infiltrating lymphocytes is correlated with favorable patient survival in lung cancer

• Published in: Scientific reports 2015-06, Vol.5 (1), p.11471-11471, Article 11471
• Main Authors: He, Yanli, Wang, Lihui, Liu, Weijun, Zhong, Jinjie, Bai, Shengbin, Wang, Zhuwen, Thomas, Dafydd G., Lin, Jules, Reddy, Rishindra M., Ramnath, Nithya, Carrott, Philip W., Lynch, William R., Orringer, Mark B., Chang, Andrew C., Beer, David G., Chen, Guoan
• Format: Article
• Language: English
• Subjects: 13; 13/105; 13/51; 13/89; 38; 38/61; 38/77; 38/79; 631/67/1612/1350; 631/67/1857; 692/308/575; Adenocarcinoma - genetics; Adenocarcinoma - immunology; Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma of Lung; AKT protein; cdc25 Phosphatases - genetics; Cell cycle; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cyclin E - genetics; Epithelial-Mesenchymal Transition - genetics; Female; G1 Phase Cell Cycle Checkpoints - genetics; Gene Expression; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Gene Silencing; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Humanities and Social Sciences; Humans; Immune response; Immunomodulation; JNK protein; Leukocyte migration; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; MAP Kinase Kinase Kinase 3 - genetics; MAP Kinase Kinase Kinase 3 - metabolism; multidisciplinary; Oncogene Proteins - genetics; Prognosis; Protein arrays; Proteins; Proto-Oncogene Proteins c-akt - metabolism; RNA, Messenger - genetics; Science; Signal Transduction; siRNA; Survival; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Tumor cell lines; Tumor cells; Tumor-infiltrating lymphocytes; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep11471

MAP3K3 is involved in both the immune response and in tumor progression. Its potential biological role in vitro in lung cancer cell lines and the association of mRNA/protein expression patterns with clinical outcome of primary lung tumors were investigated in this study. Silencing MAP3K3 using siRNA in lung cancer cell lines resulted in decreased cell proliferation, migration and invasion. These effects were associated with down-regulation of the JNK, p38, AKT and GSK3β pathways as determined using phospho-protein and gene expression array analyses. However, MAP3K3 mRNA and protein overexpression in primary lung tumors correlated significantly with favorable patient survival. Gene cluster and pathway analyses of primary tumor datasets indicated that genes positively-correlated with MAP3K3 are significantly involved in immune response rather than the cell cycle regulators observed using in vitro analyses. These results indicate that although MAP3K3 overexpression has an oncogenic role in vitro, in primary lung adenocarcinomas it correlates with an active immune response in the tumor environment that correlates with improved patient survival. MAP3K3 may potentially not only serve as diagnostic/prognostic markers for patients with lung cancer but also provide an indicator for future investigations into immunomodulatory therapies for lung cancer.