MTSS1, also known as metastasis suppressor-1, is a ubiquitously expressed intracellular protein involved in basic cellular processes such as regulating actin organization and membrane architecture. It acts as a scaffold protein for several E3 ubiquitin ligases and is involved in modulating cell-cell contacts, cell differentiation, lipid metabolism, and vesicle formation [2].

MTSS1 has been found to be downregulated in many types of cancers, including lung adenocarcinoma, prostate cancer, breast cancer, colorectal cancer, nasopharyngeal carcinoma, and gastric cancer. In lung adenocarcinoma, its downregulation leads to PD-L1 upregulation, impairment of CD8+ lymphocyte function, and enhanced tumor progression. Mechanistically, MTSS1 interacts with the E3 ligase AIP4 for PD-L1 monoubiquitination, leading to PD-L1 endocytic sorting and lysosomal degradation [1]. In breast cancer, Mtss1 knockout enhances the mammary epithelial tumor-initiating cell subpopulation, while MTSS1 suppresses tumorsphere formation by facilitating RBCK1-mediated p65 ubiquitination and degradation, thus suppressing the NF-κB signaling pathway [3]. In colorectal cancer, MTSS1 inhibits metastasis by regulating the CXCR4/CXCL12 signaling axis [4]. In nasopharyngeal carcinoma, downregulation of MTSS1 disrupts adherens junctions, leading to enhanced cell migration and invasion [5]. In gastric cancer, overexpression of MTSS1 reduces cell proliferation, migration, and invasion, and induces G2/M phase cell cycle arrest [7]. In acute leukemia, downregulation of MTSS1 gene expression at diagnosis is associated with poor outcome [6].

In conclusion, MTSS1 plays a crucial role in multiple biological processes and is involved in the development and progression of various cancers. Gene knockout or knockdown models in these studies have been instrumental in revealing its functions in different disease conditions, highlighting its potential as a therapeutic target in cancer treatment.