Stress-induced Golgiphagy sustains tumor-promoting glycosylation in breast cancer
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Updated: Nov 3, 2026

Glycan Node Analysis: A Bottom-up Approach to Glycomics
Published on: May 22, 2016
1Department of Neurology, Department of Urology, Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
Abstract:
Golgiphagy contributes to Golgi quality control, yet its regulatory mechanisms and physiological functions remain poorly understood. We identify the deubiquitinase USP28 as an upstream regulator of TM9SF3-dependent Golgiphagy. Nutrient deprivation and Golgi stress induce CRM1-dependent nuclear export of USP28, enabling its translocation to the Golgi, where it removes K48-linked ubiquitin chains from TM9SF3 to prevent its proteasomal degradation and promote Golgiphagy. TM9SF3-dependent Golgiphagy regulates glycosyltransferase abundance through selective degradation of cargo such as MGAT5, thereby maintaining glycosylation homeostasis. Genetic or pharmacological inhibition of the USP28-TM9SF3-Golgiphagy pathway disrupts glycosylation homeostasis and suppresses breast tumor growth. Together, these findings establish the USP28-TM9SF3 axis as a regulatory mechanism linking Golgiphagy to glycosylation homeostasis and breast cancer progression.
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