NIBAN1, Exploring its Roles in Cell Survival Under Stress Context.

Cell survival must quickly activate specific mechanisms that enable to detect changes in the cellular microenvironment. The impact of these cell alteration has direct consequences on cellular homeostasis. Cellular stress, as well as its regulation and implication, has been studied in different pathologies. In this sense, the alteration in NIBAN1 expression seems to act in response to different cellular disturbances. Over the years, the knowledge of NIBAN1 functions has improved, demonstrating its important cell roles, favoring the cell survival under stress context. In response to the disturbances, NIBAN1 seems to be involved in the decision-making process between cell survival and death. The increase in NIBAN1 expression has been related to cellular mechanisms that seek to minimize the damage caused to cellular homeostasis. In this review, the main biological insights attributed to the NIBAN1 gene in different cellular contexts and its role as a mediator of cellular stress are discussed.

FAM129A regulates autophagy in thyroid carcinomas in an oncogene-dependent manner.

We previously proposed that high expression of FAM129A can be used as a thyroid carcinoma biomarker in preoperative diagnostic exams of thyroid nodules. Here, we identify that FAM129A expression is increased under nutrient and growth factor depletion in a normal thyroid cell line (PCCL3), overlapping with increased expression of autophagy-related protein and inhibition of AKT/mTOR/p70S6K. Supplementation of insulin, TSH and serum to the medium was able to reduce the expression of both FAM129A and autophagy-related protein and reestablish the AKT/mTOR/p70S6K axis. To determine the direct role of FAM129A on autophagy, FAM129A was transfected into PCCL3 cells. Its overexpression induced autophagic vesicles formation, evidenced by transmission electron microscopy. Co-expression of FAM129A and mCherry-EGFP-LC3B in PCCL3 showed an increased yellow puncta formation, suggesting that FAM129Ainduces autophagy. To further confirm its role on autophagy, we knockdown FAM129A in two thyroid carcinoma cell lines (TPC1 and FTC-236). Unexpectedly, FAM129A silencing increased autophagic flux, suggesting that FAM129A inhibits autophagy in these models. We next co-transfected PCCL3 cells with FAM129A and RET/PTC1 and tested autophagy in this context. Co-expression of FAM129A and RET/PTC1 oncogene in PCCL3 cells, inhibited RET/PTC1-induced autophagy. Together, our data suggest that, in normal cells FAM129A induces autophagy in order to maintain cell homeostasis and provide substrates under starvation conditions. Instead, in cancer cells, decreased autophagy may help the cells to overcome cell death. FAM129A regulates autophagy in a cell- and/or context-dependent manner. Our data reinforce the concept that autophagy can be used as a strategy for cancer treatment.