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Acquisition of anoikis resistance through CD147 upregulation: A new mechanism underlying metastasis of hepatocellular carcinoma cells.

ABSTRACT: Acquisition of anoikis resistance is a prerequisite for the metastasis of hepatocellular carcinoma (HCC) cells. Activation of growth factor signaling pathways and rearrangement of the cytoskeleton have been reported as vital steps in this process. However, key molecules involved in anoikis resistance remain to be determined. The aim of this study was to investigate the effect of CD147 on HCC cells resistant to anoikis. The human SMMC-7221 human HCC cell line was used. Immunofluorescence was used to investigate the expression levels of CD147. Anoikis-induced cell death was assessed using trypan blue exclusion. In the present study, the results showed that SMMC-7721 HCC cells exhibited significant morphological changes when suspended in culture medium supplemented with 1% methocel and a subpopulation of cells resistant to anoikis was acquired with higher viability and invasion ability. CD147 was identified to be significantly increased in cells resistant to anoikis, when compared to the parental cells. CD147 knockdown by siRNA notably induced cell anoikis, partially through the inactivation of PI3K/Akt pathway. All of these evidence provide a novel CD147-related mechanism underlying the metastasis of HCC cells.

SUBMITTER: Ke X

PROVIDER: S-EPMC3392584 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Acquisition of anoikis resistance through CD147 upregulation: A new mechanism underlying metastasis of hepatocellular carcinoma cells.

Ke Xia X Li Ling L Dong Hong-Lin HL Chen Zhi-Nan ZN

Oncology letters 20120327 6

Acquisition of anoikis resistance is a prerequisite for the metastasis of hepatocellular carcinoma (HCC) cells. Activation of growth factor signaling pathways and rearrangement of the cytoskeleton have been reported as vital steps in this process. However, key molecules involved in anoikis resistance remain to be determined. The aim of this study was to investigate the effect of CD147 on HCC cells resistant to anoikis. The human SMMC-7221 human HCC cell line was used. Immunofluorescence was used ...[more]

PMID: 22783427

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Project description:Anoikis is a mode of apoptotic cell death, consequential to insufficient cell-matrix interactions and a critical player in tumor angiogenesis and metastasis. The events involved in tumor cell progression toward metastasis potential are mediated by integrins, which upon engagement with components of the extracellular matrix (ECM), reorganize to form adhesion complexes. Targeting apoptotic players is of immense therapeutic significance since resistance to apoptosis is not only critical in conferring therapeutic failure to standard treatment strategies, but anoikis (apoptosis upon loss of anchorage and detachment from ECM) also plays an important role in angiogenesis and metastasis. The ability to survive in the absence of adhesion to the ECM, enables tumor cells to disseminate from the primary tumor site, invade a distant site and establish a metastatic lesion. Tumor cells can escape from detachment-induced apoptosis by controlling anoikis pathways, including the extrinsic death receptor pathway and the ECM-integrin mediated cell survival pathway. Considering the functional promiscuity of individual signaling effectors, it is critical to dissect the molecular networks mechanistically driving tumor cells to evade anoikis and embark on a metastatic spread. Resistance to die via anoikis dictates tumor cell survival and provides a molecular basis for therapeutic targeting of metastatic prostate cancer. Further dissection of critical anoikis signaling events will enable the therapeutic optimization of anoikis targeting to impair prostate cancer metastasis prior to its initiation. This review will discuss the molecular understanding of anoikis regulation in the tumor microenvironment and the in vivo pharmacological implementation of a novel class of antitumor-drugs to optimize apoptotic-based therapeutic targeting, bypassing anoikis-resistance to impair prostate cancer progression to metastasis. Potential combination strategies targeting tumor vascularity (via anoikis) and impairing tumor initiation (via "classic" apoptosis), provide strong therapeutic promise for metastatic prostate cancer by preventing the onset of metastasis.

Dataset Information

Acquisition of anoikis resistance through CD147 upregulation: A new mechanism underlying metastasis of hepatocellular carcinoma cells.

Publications

Acquisition of anoikis resistance through CD147 upregulation: A new mechanism underlying metastasis of hepatocellular carcinoma cells.

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