Transmembrane (TMEM)‐176A and 176B Proteins Are Directly Linked to Cancer Pathology

Abstract

The immune system plays a role in the fight against cancer, but it has also been found to promote cancer proliferation. Two transmembrane (TMEM) proteins, TMEM176A and 176B, were reported to play a role in the immune cell function. Recent reports showed that TMEM176A mRNA transcripts are highly elevated in liver cancer or kidney proteinuria, while increased TMEM176B mRNA transcripts are detected in tolerated tissue allografts. We set out to determine the functional relationship between TMEM176A and 176B, as well as to provide any direct evidence that one or both proteins are linked to cancer pathology. Real‐time QPCR revealed a diverse mRNA expression pattern for TMEM176A and 176B. Co‐immunoprecipitation showed that both proteins physically interact. TMEM176A and 176B protein expression analysis showed significant elevation in lymphoma compared to normal non‐cancerous tissues. In lung cancer, the protein levels of TMEM176A were also significantly increased. Interestingly, the protein expression ratio of TMEM176A over TMEM176B, revealed significant differences between normal and cancer tissues of the breast, lymph, skin, and liver. Our findings indicate that TMEM176A and 176B proteins physically interact, and that the protein level of TMEM176B is intimately linked to that of TMEM176A protein in distinct cancer tissues.