Abstract 1949: P38MAPK plays a tumor suppressive role through differentiation of ALDHhigh/CD44high tumor iniating cells in primary human lung adenocarcinoma

Abstract

Abstract The p38 MAPK cascade regulates body responses to a wide range of stress stimuli in a context-dependent and tissue-specific manner. The isoform p38alpha (p38) mediates both tumor suppressive and tumor-supportive functions in different cancer models. However, its role in lung cancer is not clear. Since EGFR is frequently mutated in lung adenocarcinomas in non-smoking women and p38 is a downstream target of EGFR signaling, it is possible that p38 plays a tumor-supportive role. Using immunohistochemistry to analyze nuclear activated p38 expression in 90 lung adenocarcinomas, we observed p38 expression was significantly associated with well differentiated compared to poorly-differentiated carcinomas (p<0.001) and better patient outcome (p=0.019, disease-free survival; p=0.03, overall survival). In vitro p38 suppression in lung cancer cell lines did not lead to enhanced cell death. On the other hand, p38 suppression alone or in combination with EGFR inhibition led to increased CD44high/ALDHhigh lung tumor initiating cells (TIC); isolated lung TIC also showed higher p38 expression. Together, the data implicate p38 plays a tumor suppressive role in lung cancer by driving tumor cell differentiation. Disrupting pathways that inhibit p38 expression or enhancement of p38 expression might be useful for lung cancer treatment. Citation Format: Jing Liu, Lai-han Leung, Zhi-jie Xiao, Vicky PC Tin, Maria Pik Wong. P38MAPK plays a tumor suppressive role through differentiation of ALDHhigh/CD44high tumor iniating cells in primary human lung adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1949. doi:10.1158/1538-7445.AM2014-1949