The Diverse Role of CUB and Sushi Multiple Domains 1 (CSMD1) in Human Diseases

Abstract

CUB and Sushi Multiple Domains 1 (CSMD1), a tumour suppressor gene, encodes a large membrane-bound protein including a single transmembrane domain. This transmembrane region has a potential tyrosine phosphorylation site, suggesting that CSMD1 is involved in controlling cellular functions. Although the specific mechanisms of action for CSMD1 have not yet been uncovered, it has been linked to a number of processes including development, complement control, neurodevelopment, and cancer progression. In this review, we summarise CSMD1 functions in the cellular processes involved in the complement system, metastasis, and Epithelial mesenchymal transition (EMT) and also in the diseases schizophrenia, Parkinson's disease, and cancer. Clarifying the association between CSMD1 and the aforementioned diseases will contribute to the development of new diagnosis and treatment methods for these diseases. Recent studies in certain cancer types, e.g., gastric cancer, oesophageal cancer, and head and neck squamous cell carcinomas, have indicated the involvement of CSMD1 in response to immunotherapy.

Keywords: CSMD1; Parkinson’s disease; cancer; complement system; schizophrenia.

Figure 1

Schematic illustration of the CUB and Sushi Multiple Domains 1 (CSMD1) gene and protein structures.

Figure 2

Frequency and type of genetic alterations at the CSMD1 locus in different cancer types.

Figure 3

Summary of CSMD1-mediated functions.

Figure 4

Overview of complement system and CSMD1.

Figure 5

CSMD1 differential gene expression in normal and tumour tissues. CSMD1 is overexpressed in a number of tumour types compared to normal tissue, with AML and liver being the highest. However, CSMD1 expression is not strongly observed in renal and prostate tumours. A Mann–Whitney U test was performed to mark the significant difference in expression between normal and tumour samples depicted by red colour.

Figure 6

Brief summary of EMT, MET, and CSMD1.