FAM134B'nin biyolojik işlevleri ve kanserle ilişkisi

Hepatocellular Carcinoma (HCC) is a major health problem worldwide and cause thousands of deaths each year. HCC development is mostly stemmed from the cirrhotic liver where hepatocytes escape cellular senescence to gain immortality. Our group has previously defined the expressional decrease of FAM134B as a hallmark for immortalization. Later, FAM134B was shown to be a receptor that mediates degradation of Endoplasmic Reticulum fragments through the autophagosome. However, how these properties are associated with development of cancer remains largely unknown. Therefore, we aimed to investigate the functional characterization of FAM134B in the context of physiology and cancer. Using in vitro and in vivo models, expressional changes of FAM134B variants were tested in response to various cellular stresses such as fasting, ER-stress, and inhibition of proteasome machinery. In the context of cancer, the expression of FAM134B variants was screened using databases in different cancer types. The effect of FAM134B variants on HCC tumor formation was evaluated by in vivo xenograft model. The findings have shown that there are at least two transcriptional isoforms in human, and bovine, and at least six isoforms in mouse. Starvation stimulated short FAM134B-2 expression in the skeletal and cardiac muscles as well as in the liver of Fam134b+/+ mice. Fasted Fam134b-/- mice yielded significant changes in body weight, serum biochemistry and liver transcriptome. Ectopic expression of FAM134B variants altered ER-stress response in vitro and suppressed xenograft tumor growth in vivo. Finally, short FAM134B variant was found to be significantly changed variant during the development of different tumors, including HCC. In conclusion, the short and long FAM134B isoforms were shown mediate different functions in physiology and cancer, play an important role in energy metabolism; and lastly, the short FAM134B-2 variant is the most altered in various cancers.