TUSC3, short for Tumor Suppressor Candidate 3, is a gene located on chromosome 8p22. It encodes a 34 kD protein which is a subunit of the oligosaccharyl transferase responsible for the N-glycosylation of nascent proteins in the endoplasmic reticulum [1]. It is also involved in magnesium transport and homeostasis as an Mg2+-transporter, which is crucial for learning and memory, embryonic development, and testis maturation [1]. Dysregulation of TUSC3 has been linked to various diseases, especially cancer, highlighting its biological importance. Genetic models, such as gene knockout models, can be valuable for studying its functions.

In cervical squamous cell carcinoma, down-regulation of TUSC3 promoted cell metastasis via the AKT signalling pathway, suggesting it may serve as a prognostic marker and potential target [2]. In hepatocellular carcinoma, decreased TUSC3 expression led to enhanced cell proliferation and migration, and it regulated epithelial-mesenchymal transition (EMT) through the LIPC/AKT axis [3]. In colorectal cancer, TUSC3 was found to promote the formation of cellular stemness and induce drug resistance via the Hedgehog signalling pathway [4]. Also, its promoter methylation in peripheral blood cells shows promise as a biomarker for CRC diagnosis [5]. In clear cell renal cell carcinoma, TUSC3 expression was downregulated, and it may inhibit the progression of the disease, potentially serving as a tumor marker for early diagnosis and prognosis [6]. In glioblastoma, epigenetic reactivation of TUSC3 can reprogram sensitivity to temozolomide regardless of MGMT promoter methylation status [7].

In conclusion, TUSC3 is essential for protein N-glycosylation and magnesium homeostasis. Through gene knockout or other loss-of-function models in various cancers, it has been revealed that TUSC3 plays significant roles in cancer cell proliferation, invasion, metastasis, drug resistance, and EMT. Understanding TUSC3 functions can provide new insights into cancer mechanisms and potential therapeutic targets. Additionally, its potential as a biomarker in cancer diagnosis and as a therapeutic target in XMEN disease further emphasizes its importance in biomedical research.