Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/36457
Title: Dysregulation of apoptosis in hepatocellular carcinoma cells
Author: Fabregat Romero, Isabel
Keywords: Apoptosi
Càncer de fetge
Apoptosis
Liver cancer
Issue Date: Feb-2009
Publisher: Baishideng Publishing Group
Abstract: Hepatocellular carcinoma (HCC) is a major health problem, being the sixth most common cancer world-wide. Dysregulation of the balance between proliferation and cell death represents a pro-tumorigenic principle in human hepatocarcinogenesis. This review updates the recent relevant contributions reporting molecular alterations for HCC that induce an imbalance in the regulation of apoptosis. Alterations in the expression and/or activation of p53 are frequent in HCC cells, which confer on them resistance to chemotherapeutic drugs. Many HCCs are also insensitive to apoptosis induced either by death receptor ligands, such as FasL or TRAIL, or by transforming growth factor-beta (TGF-beta). Although the expression of some pro-apoptotic genes is decreased, the balance between death and survival is dysregulated in HCC mainly due to overactivation of anti-apoptotic pathways. Indeed, some molecules involved in counteracting apoptosis, such as Bcl-XL, Mcl-1, c-IAP1, XIAP or survivin are over-expressed in HCC cells. Furthermore, some growth factors that mediate cell survival are up-regulated in HCC, as well as the molecules involved in the machinery responsible for cleavage of their pro-forms to an active peptide. The expression and/or activation of the JAK/STAT, PI3K/AKT and RAS/ERKs pathways are enhanced in many HCC cells, conferring on them resistance to apoptotic stimuli. Finally, recent evidence indicates that inflammatory processes, as well as the epithelial-mesenchymal transitions that occur in HCC cells to facilitate their dissemination, are related to cell survival. Therefore, therapeutic strategies to selectively inhibit anti-apoptotic signals in liver tumor cells have the potential to provide powerful tools to treat HCC.
Note: Reproducció del document publicat a: http://dx.doi.org/10.3748/wjg.15.513
It is part of: World Journal of Gastroenterology, 2009, vol. 15, num. 5, p. 513-520
Related resource: http://dx.doi.org/10.3748/wjg.15.513
URI: http://hdl.handle.net/2445/36457
ISSN: 1007-9327
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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