Two decades ago, following a systematic screening of LOH regions on chromosome 8p22, TUSC3 has been identified as a candidate tumor suppressor gene in ovarian, prostate and pancreatic cancers. Since then, a growing body of evidence documented its clinical importance in various other types of cancers, and first initial insights into its molecular function and phenotypic effects have been gained, though the precise role of TUSC3 in different cancers remains unclear. As a part of the oligosaccharyltransferase complex, TUSC3 localizes to the endoplasmic reticulum and functions in final steps of N-glycosylation of proteins, while its loss evokes the unfolded protein response. We are still trying to figure out how this mechanistic function is reconcilable with its varied effects on cancer promotion. In this review, we focus on cancer-related effects of TUSC3 and envisage a possible role of TUSC3 beyond endoplasmic reticulum.

Department of Histology and Embryology Faculty of Medicine Masaryk University Kamenice 126 3 625 00 Brno Czech Republic

Department of Translational Oncology National Center for Tumor Diseases Im Neuenheimer Feld 460 69120 Heidelberg Germany

German Cancer Research Center Heidelberg Germany

International Clinical Research Center St Anne's University Hospital Brno Pekařská 53 65691 Brno Czech Republic

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Intact cell mass spectrometry coupled with machine learning reveals minute changes induced by single gene silencing