Open AccessGenomic abnormalities and signal transduction dysregulation in malignant mesothelioma cells
Author(s) -
Sekido Yoshitaka
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01336.x
Subject(s) - cancer research , biology , merlin (protein) , protein kinase b , signal transduction , receptor tyrosine kinase , carcinogenesis , mapk/erk pathway , pi3k/akt/mtor pathway , epigenetics , malignant transformation , microbiology and biotechnology , kinase , cancer , suppressor , genetics , gene
Malignant mesothelioma (MM) is a tumor with poor prognosis associated with asbestos exposure. While it remains to be clarified how asbestos fibers confer genetic/epigenetic alterations and induce cellular transformation in normal mesothelial cells, the understanding of key molecular mechanisms of MM cell development, proliferation, and invasion has progressed. MM shows frequent genetic inactivation of tumor suppressor genes of p16 INK4a / p14 ARF and neurofibromatosis type 2 ( NF2 ) which encodes Merlin, and epigenetic inactivation of RASSF1A . However, no frequent mutations of well‐known oncogenes such as K‐RAS and PIK3CA have been identified. Activation of multiple receptor tyrosine kinases including the epidermal growth factor receptor (EGFR) family and MET, and subsequent deregulations of mitogen‐activated protein kinase (MAPK) and phosphatidylinositol‐3‐kinase (PI3K)–AKT signaling cascades are frequently observed in most MM cells. The tumor suppressive function of Merlin in MM cells is also being investigated by dissecting its possible downstream signaling cascade called the Hippo pathway. Further comprehensive delineation of dysregulated signaling cascades in MM cells will lead to identification of key addiction pathways for cell survival and proliferation of MM cells, which strongly promote establishment of a new molecular target therapy for MM. ( Cancer Sci 2009)