[3] NUT protein facilitates the acetylation of chromatin (i.e. DNA-protein bundles) by histone acetyltransferase EP300 in testicular spermatids (cells that mature into sperms).
It is generally accepted that the BRD4-NUT protein promotes these neoplasms by maintaining their neoplastic cells in a perpetually undifferentiated, proliferative state.
However, subsequent studies defined these carcinomas based on the presence of a NUT fusion gene in their malignant cells.
As so defined, this malignancy occurs in individuals of all ages and, while most commonly developing in the cited respiratory, gastrointestinal, and mediastinal areas, occasionally develops in the salivary glands, pancreas, urinary bladder, retroperitoneum (i.e. space behind the peritoneum of the abdominal cavity),[8] endometrium, kidneys, ovaries, and other organs.
Expression of the NUTM1 (fusion) protein was observed in 25 poroma and 6 porocarcinoma cases but not in a wide range of other skin tumor types.
Studies on cultured immortalized human dermal keratinocyte (i.e. HDK) and mouse embryonic fibroblast NIH-3T3 cell lines found that the YAP1-NUTM1 and WWTR1-NUTM1 fusion genes stimulated the anchorage-independent growth of NIH-3T3 cells and activated a transcriptional enhancer factor family member (i.e. TEAD family) reporter gene.
[16] The TEAD family in mammals includes four members, TEAD1, TEAD2, TEAD3, and TEAD4 that are transcription factors, i.e. proteins that regulate the expression of various genes.
TEAD family proteins have been found to promote the development, progression, and/or metastasis of various cancer types[17][18] and, based on the studies just cited,[17] are thought to do so in poromas and porocarcinomas.
However, further studies are needed to confirm this association and determine if TEAD family transcription factors may be useful targets for treating the porocarcinomas.