Insulinoma-associated protein 1 (INSM1): a potential biomarker and therapeutic target for neuroendocrine tumors

Background Insulinoma-associated protein 1 (INSM1), a transcriptional regulator with a zinc-finger DNA-binding domain, has been validated as a cytoplasmic marker for neuroendocrine differentiation of tumor cells. Next to its abundant expression in the fetal pancreas, it is expressed in brain tumors, pheochromocytomas, medullary thyroid carcinomas, insulinomas and pituitary and small-cell lung carcinomas. INSM1 is not expressed in normal adult tissues and/or most non-neuroendocrine tumors. It regulates various downstream signaling pathways, including the Sonic Hedgehog, PI3K/AKT, MEK/ERK1/2, ADK, p53, Wnt, histone acetylation, LSD1, cyclin D1, Ascl1 and N-Myc pathways. Although INSM1 appears to be a subtle and specific biomarker for neuroendocrine tumors, its role in tumor development has remained unclear. Conclusions Here, we highlight INSMI expression, as well as its diagnostic significance and use as a therapeutic target in various neuroendocrine tumors. Targeting signaling pathways or gene expression alterations associated with INSM1 expression may be instrumental for the design of novel therapeutic strategies for neuroendocrine tumors.