TUSC3, also known as Tumor Suppressor Candidate 3, is a gene located on chromosome 8p22. It encodes a 34 kD protein that is a subunit of the oligosaccharyl transferase complex responsible for the N-glycosylation of nascent proteins in the endoplasmic reticulum. Dysfunction or deletion of TUSC3 can lead to endoplasmic reticulum stress. It has been associated with multiple biological processes such as magnesium transport and homeostasis, and is also linked to autosomal recessive mental retardation [1].

TUSC3 has shown variable roles in different cancers. In cervical squamous cell carcinoma, decreased TUSC3 expression promotes cell proliferation and invasion via the AKT signalling pathway [2]. In colorectal cancer, TUSC3 can promote the formation of cellular stemness and drug resistance through the Hedgehog signalling pathway [3]. In hepatocellular carcinoma, down-regulation of TUSC3 promotes epithelial-mesenchymal transition (EMT) and cancer progression through the LIPC/AKT axis [4]. In clear cell renal cell carcinoma, TUSC3 expression is downregulated, and it may inhibit cancer progression [5]. However, in another study on colorectal cancer, overexpression of TUSC3 promoted cancer progression and EMT through WNT/β-catenin and MAPK signalling [6].

In conclusion, TUSC3 plays a crucial role in protein N-glycosylation and is involved in multiple biological processes. Its dysregulation is associated with various cancers, and the study of TUSC3 in gene knockout or other loss-of-function models has helped to reveal its complex roles in cancer development and progression, providing potential targets for cancer diagnosis and treatment.