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

Abstract

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.

ARHGEF4 predicts poor prognosis and promotes cell invasion by influencing ERK1/2 and GSK-3α/β signaling in pancreatic cancer

“…Src is found at the crossroads of several signaling pathways, including Ras/Raf/ERK1/2 (31)(32)(33), and it promotes cell proliferation, survival, invasion, migration and angiogenesis. The p38 and GSK-3α/β pathways promote the proliferation, migration, and invasion of lung cancer cells (34). In PDAC cells, an antioxidant defense enzyme, Prdx1, is associated with the formation of membrane protrusions through the modulation of p38-MAPK activity, which in turn promotes cell invasion (35).…”

MEKK3 Sustains EMT and Stemness in Pancreatic Cancer by Regulating YAP and TAZ Transcriptional Activity

“…In particular, MEKK3 induced proliferation, migration and invasion of lung cancer cells, through the activation of AKT and GSK3β signaling pathways (36), metastasis and survival of breast cancer cells (37), as well as chemoresistance of ovarian cancer cells (38,39). MEKK3 has shown clinical relevance in esophageal squamous cell carcinoma, where the combination of its overexpression combined to lymph-node positivity has been shown to be a negative prognostic factor (40).…”

Overexpression of FAM83H-AS1 indicates poor patient survival and knockdown impairs cell proliferation and invasion via MET/EGFR signaling in lung cancer

“…These subtypes represent distinct clinical entities, typically requiring different treatment options. Among these histological subtypes there exist cancers with diverse clinical outcomes, revealing heterogeneity in disease aggressiveness and underlying molecular alterations 3 4 5 . Indeed, the poor prognosis associated with lung cancer (15.7–18% 5-year survival) is related to the complex cellular, molecular and tumor microenvironment factors that impart a unique biological basis to an individual’s disease 2 .…”