[Functional Analysis of Apoptosis Signal-regulating Kinase Family in a Murine Model of Tumor Metastasis].

Abstract

Stress-responsive signaling pathways convert cellular stresses into various physiological responses, such as cell proliferation, apoptosis, and inflammation. Signal pathway dysfunction thus induces abnormal cellular behaviors that may lead to tumorigenesis and tumor progression, including metastasis. Tumor metastasis is the spread of tumor cells from primary lesions to other distant tissues/organs. Several types of murine model which mimic the progression of human cancer have been established for preclinical studies to understand the biology of cancer. Mitogen-activated protein kinase (MAPK) cascades are one of the stress-responsive signaling pathways and are intricately involved in both tumor promotion and suppression. Here, we present the diverse roles of apoptosis signal-regulating kinase (ASK) family molecules in tumor formation and progression. ASK family is a member of MAPK kinase kinase (MAP3K) family in the c-Jun N-terminal kinase (JNK) and p38 MAPK pathways and comprises three family members, ASK1, ASK2, and ASK3. Accumulating evidence indicates that ASK1 controls tumorigenesis through the regulation of innate immunity and apoptosis. ASK2 also regulates tumorigenesis via apoptosis. Furthermore, analysis of the experimental lung metastasis model in mice suggests that host ASK1 deficiency attenuates tumor lung metastasis. In this symposium review, we discuss the potential roles of ASK family in the context of tumor metastasis.