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Cytoplasmic/Nuclear Shuttling and Tumor Progression
Author(s) -
WANG SHAOCHUN,
HUNG MIENCHIE
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1339.002
Subject(s) - biology , transcription factor , microbiology and biotechnology , subcellular localization , receptor tyrosine kinase , metastasis , signal transduction , protein kinase b , cell growth , cancer cell , cancer research , cancer , cytoplasm , gene , genetics
A bstract : Protein localization is a highly dynamic biological process. To ensure a proper cellular function, the spatial distribution of different proteins needs to be delicately regulated and coordinated. In cancer, this process is tightly correlated with the outcome of cell proliferation and the response to apoptotic stress. Here we summarize our recent studies regarding the role of subcellular trafficking on cancer cell growth through an AKT‐independent regulation of the forkhead transcription factor and, on cancer metastasis, through the regulated localization and subsequent protein degradation of the Snail protein, a key transcription factor involved in epithelial‐mesenchymal transition (EMT). In both cases, cellular signaling pathways mediated by distinct protein kinases modulate the appropriate protein localization and functioning. Finally, we address a novel translocation pathway for tyrosine kinase receptors between the cell membrane and the nucleus. We demonstrate that the ErbB family proteins are also expressed in the nucleus and can function as transcriptional regulators. Using a genomic approach, we have identified a number of the target genes regulated by this pathway that are closely related to cancer cell proliferation and metastasis. Our findings, together with the seminal discoveries by other groups, highlight the importance of protein localization in cancer biology and its potential to be a therapeutic target for cancer.