LIM domain only 1: an oncogenic transcription cofactor contributing to the tumorigenesis of multiple cancer types

Abstract

The LIM domain only 1 (LMO1) gene belongs to the LMO family of genes that encodes a group of transcriptional cofactors. This group of transcriptional cofactors regulates gene transcription by acting as a key “connector” or “scaffold” in transcription complexes. All LMOs, including LMO1, are important players in the process of tumorigenesis. Unique biological features of LMO1 distinct from other LMO members, such as its tissue-specific expression patterns, interacting proteins, and transcriptional targets, have been increasingly recognized. Studies indicated that LMO1 plays a critical oncogenic role in various types of cancers, including T-cell acute lymphoblastic leukemia, neuroblastoma, gastric cancer, lung cancer, and prostate cancer. The molecular mechanisms underlying such functions of LMO1 have also been investigated, but they are currently far from being fully elucidated. Here, we focus on reviewing the current findings on the role of LMO1 in tumorigenesis, the mechanisms of its oncogenic action, and the mechanisms that drive its aberrant activation in cancers. We also briefly review its roles in the development process and non-cancer diseases. Finally, we discuss the remaining questions and future investigations required for promoting the translation of laboratory findings to clinical applications, including cancer diagnosis and treatment.

LMO family gene polymorphisms and Wilms tumor susceptibility in Chinese children: a five-center case-control study

“…The LMO family genes consist of four members, LMO1-4 , each of which has been established to be responsible not only for many normal developmental processes but also for the initiation and development of various human cancers, including T-cell acute lymphoblastic leukemia, neuroblastoma, lung cancer, colorectal cancer, and breast cancer [ 21 , 22 , 25 , 30 – 32 ]. The products of LMO family genes share a common two-tandem LIM domain structure, a highly conserved and cysteine-rich zinc binding motif without additional domains, mediating protein‒protein interactions instead of binding to DNA directly [ 33 ]. Thus, LMO proteins were previously regarded as adapter molecules for the formation of new versatile multiprotein complexes, which are crucial for participation in various cellular processes, including cell proliferation, cell self-renewal, differentiation, and metastasis [ 21 , 34 ].…”