Hepatocellular carcinoma(HCC)has emerged as one of the most commonly diagnosed forms of human cancer;yet,the mechanisms underlying HCC progression remain unclear.Unlike other cancers,systematic chemotherapy is not eff...Hepatocellular carcinoma(HCC)has emerged as one of the most commonly diagnosed forms of human cancer;yet,the mechanisms underlying HCC progression remain unclear.Unlike other cancers,systematic chemotherapy is not effective for HCC patients,while surgical resection and liver transplantation are the most viable treatment options.Thus,identifying factors or pathways that suppress HCC progression would be crucial for advancing treatment strategies for HCC.The murine double minute 2(MDM2)-p53 pathway is impaired in most of the cancer types,including HCC,and MDM2 is overexpressed in approximately 30%of HCC.Overexpression of MDM2 is reported to be well correlated with metastasis,drug resistance,and poor prognosis of multiple cancer types,including HCC.Importantly,these correlations are observed even when p53 is mutated.Indeed,p53-independent functions of overexpressed MDM2 in cancer progression have been suitably demonstrated.In this review article,we summarize potential effectors of MDM2 that promote or suppress cancer metastasis and specifically discuss the p53-independent roles of MDM2 in liver cancer metastasis from clinical as well as biological perspectives.展开更多
Liver cancer remains one of the most common human cancers with a high mortality rate. Therapies for hepatocellular carcinoma (HCC) remain ineffective, due to the heterogeneity of HCC with regard to both the etiology a...Liver cancer remains one of the most common human cancers with a high mortality rate. Therapies for hepatocellular carcinoma (HCC) remain ineffective, due to the heterogeneity of HCC with regard to both the etiology and mutation spectrum, as well as its chemotherapy resistant nature;thus surgical resection and liver transplantation remain the gold standard of patient care. The most common etiologies of HCC are extrinsic factors. Humans have multiple defense mechanisms against extrinsic factor-induced carcinogenesis, of which tumor suppressors play crucial roles in preventing normal cells from becoming cancerous. The tumor suppressor p53 is one of the most frequently mutated genes in liver cancer. p53 regulates expression of genes involved in cell cycle progression, cell death, and cellular metabolism to avert tumor development due to carcinogens. This review article mainly summarizes extrinsic factors that induce liver cancer and potentially have etiological association with p53, including aflatoxin B1, vinyl chloride, non-alcoholic fatty liver disease, iron overload, and infection of hepatitis viruses.展开更多
基金supported by NIH 1-R01-CA174735-01A1(T.I.)and 5-P30-CA168524-02(PI:Roy A.Jensen)grants.
文摘Hepatocellular carcinoma(HCC)has emerged as one of the most commonly diagnosed forms of human cancer;yet,the mechanisms underlying HCC progression remain unclear.Unlike other cancers,systematic chemotherapy is not effective for HCC patients,while surgical resection and liver transplantation are the most viable treatment options.Thus,identifying factors or pathways that suppress HCC progression would be crucial for advancing treatment strategies for HCC.The murine double minute 2(MDM2)-p53 pathway is impaired in most of the cancer types,including HCC,and MDM2 is overexpressed in approximately 30%of HCC.Overexpression of MDM2 is reported to be well correlated with metastasis,drug resistance,and poor prognosis of multiple cancer types,including HCC.Importantly,these correlations are observed even when p53 is mutated.Indeed,p53-independent functions of overexpressed MDM2 in cancer progression have been suitably demonstrated.In this review article,we summarize potential effectors of MDM2 that promote or suppress cancer metastasis and specifically discuss the p53-independent roles of MDM2 in liver cancer metastasis from clinical as well as biological perspectives.
文摘Liver cancer remains one of the most common human cancers with a high mortality rate. Therapies for hepatocellular carcinoma (HCC) remain ineffective, due to the heterogeneity of HCC with regard to both the etiology and mutation spectrum, as well as its chemotherapy resistant nature;thus surgical resection and liver transplantation remain the gold standard of patient care. The most common etiologies of HCC are extrinsic factors. Humans have multiple defense mechanisms against extrinsic factor-induced carcinogenesis, of which tumor suppressors play crucial roles in preventing normal cells from becoming cancerous. The tumor suppressor p53 is one of the most frequently mutated genes in liver cancer. p53 regulates expression of genes involved in cell cycle progression, cell death, and cellular metabolism to avert tumor development due to carcinogens. This review article mainly summarizes extrinsic factors that induce liver cancer and potentially have etiological association with p53, including aflatoxin B1, vinyl chloride, non-alcoholic fatty liver disease, iron overload, and infection of hepatitis viruses.
