The Role Of TXNDC5 In Tumor Cell Ischemic Reaction

Thioredoxin domain containing protein5(TXNDC5) is originally identified as a member of the thioredoxin (Trx) domain-containing family of proteins.TXNDC5have shown multiple functional characteristics, including cell proliferation, apoptosis, invasion, cell cycle and angiogenesis. Recent studies showed that TXNDC5can act as a stress survival factor, an insulin regulator factor and a nitration reaction factor. TXNDC5is highly expressed in cancers such as gastric cancer, lung cancer, and liver cancer. Serum starvation reduces basal cellular activities and is one of the most commonly used methods in studying molecular mechanisms involved in protein degradation, cellular stress responses, autophagy, apoptosis Here we investigated the role of TXNDC5in human cervical carcinoma HeLa cell line and human breast cancer MCF7cell line in response to the serum starvation.We found that serum starvation induced the proliferation inhibition of HeLa cell, and during this process, the protein level of TXNDC5was strikingly upregulated, while the mRNA level of TXNDC5was almost unchanged. The TXNDC5mRNA stability was not affected by serum starvation. However, preotin translation inhibitor cycloheximide abolished serum starvation-induced TXNDC5protein upregulation. Therefore, we speculate that serum starvation might enhance the translation efficiency of TXNDC5protein, which resulted in the upregulation of TXNDC5protein level. Different from that in HeLa cell, the protein level of TXNDC5was affected by cell density in MCF7cell. At low confluence(5%), the protein level of TXNDC5was lower. At moderate confluence(30%-60%), serum starvation induced the proliferation inhibition of MCF7cell, meanwile both mRNA and protein level of TXNDC5increased. Conversely at low confluence(5%), serum starvation down regulated the protein level of TXNDC5. These results indicate that the response to serum starvation varies with different cell types. Further results showed that in Hela cell cultured in medium containing10%FBS, over-expression of TXNDC5had no effect on cell proliferation, while inhibition of TXNDC5slightly reduced the cell proliferation. However, suppression of TXNDC5attenuated the proliferation inhibition of HeLa cell induced by serum starvation, mildly increased the proportion of S phase in cell cycle, and had no effect on cell apoptosis.In summary, the mechanism of TXNDC5expression regulation in response to serum starvation might be different in different cell types. TXNDC5may promote proliferation in HeLa cell cultured in medium with normal serum concentration, but mediated serum starvation-induced inhibition of HeLa cell proliferation. The underlined mechanism needed to be further explored. Our results help to understand the functional role of TXNDC5and its mechanism in tumor cells.