A multi-target protein of hTERTR-FAM96A presents significant anticancer potent in the treatment of hepatocellular carcinoma.

Abstract

The abilities to escape apoptosis induced by anticancer drugs are an essential factor of carcinogenesis and a hallmark of resistance to cancer therapy. In this study, we identified hTERTR-FAM96A (human telomerase reverse transcriptase-family with sequence similarity 96 member A) as a new efficient agent for apoptosome-activating and anti-tumor protein and investigated the potential tumor suppressor function in hepatocellular carcinoma. The hTERTR-FAM96A fusion protein was constructed by genetic engineering and its anticancer function of hTERTR-FAM96A was explored in vitro and in vivo by investigating the possible preclinical outcomes. Effects of hTERTR-FAM96A on improvement of apoptotic sensitivity and inhibition of migration and invasion were examined in cancer cells and tumors. Our results showed that the therapeutic effects of hTERTR-FAM96A were highly effective for inhibiting tumor growth and inducing apoptosis of hepatocellular carcinoma cells in H22-bearing nude mice. The hTERTR-FAM96A fusion protein could specifically bind with Apaf-1 and hTERT, which further induced apoptosis of hepatocellular carcinoma cells and improved apoptosis sensitivity. Our results indicated that hTERTR-FAM96A treatment enhanced cytotoxic effects by upregulation of cytotoxic T lymphocyte responses, interferon-γ release, and T lymphocyte infiltration. In addition, hTERTR-FAM96A led to tumor-specific immunologic cytotoxicity through increasing apoptotic body on hepatocellular tumors. Furthermore, hTERTR-FAM96A dramatically inhibited tumor growth, reduced death rate, and prolonged mice survival in hepatocellular carcinoma mice derived from three independent hepatocellular carcinoma mice cohorts compared to control groups. In summary, our data suggest that hTERTR-FAM96A may serve as an efficient anti-tumor agent for the treatment of hepatocellular carcinoma.

• Authors: Meng-Yu Zhang, Jie-Ping Wang
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 39 Issue 4 Pg. 1010428317698341 (Apr 2017) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 28443470 (Publication Type: Journal Article)

Chemical References

• CIAO2A protein, human
• Carrier Proteins
• Metalloproteins
• Oncogene Proteins, Fusion
• TERT protein, human
• Telomerase

Topics

• Animals
• Apoptosis (genetics)
• Carcinoma, Hepatocellular (genetics, pathology, therapy)
• Carrier Proteins (genetics, therapeutic use)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Genetic Therapy
• Genetic Vectors
• Humans
• Liver Neoplasms (genetics, pathology, therapy)
• Metalloproteins
• Mice
• Oncogene Proteins, Fusion (genetics, therapeutic use)
• Telomerase (genetics, therapeutic use)
• Xenograft Model Antitumor Assays