Institute of Research and Development, Duy Tan University, Da Nang, 550000, Vietnam.
Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.
Cell Oncol (Dordr). 2020 Jun;43(3):367-376. doi: 10.1007/s13402-020-00505-9. Epub 2020 Mar 26.
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.
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.
胰岛素瘤相关蛋白 1（INSM1）是一种具有锌指 DNA 结合域的转录调节因子，已被验证为肿瘤细胞神经内分泌分化的细胞质标志物。除了在胎儿胰腺中大量表达外，它还在脑肿瘤、嗜铬细胞瘤、甲状腺髓样癌、胰岛素瘤以及垂体和小细胞肺癌中表达。INSM1 在正常成人组织和/或大多数非神经内分泌肿瘤中不表达。它调节各种下游信号通路，包括 Sonic Hedgehog、PI3K/AKT、MEK/ERK1/2、ADK、p53、Wnt、组蛋白乙酰化、LSD1、cyclin D1、Ascl1 和 N-Myc 通路。尽管 INSM1 似乎是神经内分泌肿瘤的一个微妙而特异的生物标志物，但它在肿瘤发展中的作用仍不清楚。
在这里，我们重点介绍 INSMI 的表达及其在各种神经内分泌肿瘤中的诊断意义和作为治疗靶点的用途。针对与 INSM1 表达相关的信号通路或基因表达改变可能是设计神经内分泌肿瘤新型治疗策略的关键。
