Part of the book: Hepatocellular Carcinoma
HCC is one of the most common cancers worldwide with high prevalence, recurrence, and lethality. The curative rate is not satisfactory. LAPTM4B is a novel driver gene of HCC first indentified by our group. It is over-expressed in 87.3% of HCC. The expression levels of the encoded LAPTM4B-35 protein in HCC is also over-expressed in 86.2% of HCC and shows a significant positive correlation with pathological grade, metastasis, and recurrence, and a negative correlation with postoperative overall- and cancer free- survival of HCC patients. Moreover, HCC cells showing high expression of LAPTM4B-35 show a strong tendency to metastasize and enhanced drug resistance. Overexpression of this gene promotes tumorigenesis, faster growth of human HCC xenografts and metastasis in nude mice, and leads to anti-apoptosis, deregulation of proliferation, enhancement of migration and invasion, as well as multi-drug resistance. In addition, overexpression of LAPTM4B-35 leads to accumulation of a number of oncoproteins and to down-regulation of a number of tumor suppressing proteins. By contrary, knockdown of endogenous LAPTM4B-35 via RNAi results in remarkable inhibition of xenograft growth and metastasis of human HCC in nude mice. Also, RNAi knockdown of LAPTN4B-35 can reverse the cellular and molecular malignant phenotypes noted above.
Part of the book: Recent Advances in Liver Diseases and Surgery