Molecular¹ microbiologists at the University of Southern California (USC) have uncovered intricate（复杂的） regulatory mechanisms³ within the cell that could lead to novel therapeutics for the treatment of cancer and other diseases. Their findings, which have long-standing significance in the basic understanding of cell biology, appear in the journal Nature Cell Biology. "Our research reveals a new regulatory mechanism² that coordinates⁴ two distinct intracellular processes that are critical to cellular⁵ homeostasis（自动调节） and disease development," said Chengyu Liang, M.D., Ph.D., a member of the USC Norris Comprehensive Cancer Center and principal investigator⁶ of the study.

 

The endoplasmic reticulum (ER内质网) and Golgi apparatus⁷ are cellular organelles in eurkaryotic organisms where proteins are synthesized and packaged for secretion⁸ through the body. The trafficking of proteins between the ER and Golgi must be tightly modulated⁹ to maintain the health of the cell and prevent diseases like cancer from taking hold.

 

"Interest in the role of ER-Golgi network during cancer cell death has been gaining momentum," said Shanshan He, Ph.D., research associate at the Keck School of Medicine of USC and one of the study's first authors. "In this study, we identified a novel regulatory factor for the Golgi-ER retrograde（倒退的） transport and a new mechanistic connection between the physiological¹⁰ trafficking and the autophagic transportation of cellular material."

 

The researchers discovered that the UV irradiation resistance-associated gene¹¹ protein (UVRAG), which has been implicated¹² in the suppression of colon¹³ and breast cancer, coordinates trafficking of proteins between the ER and Golgi apparatus and also autophagy（自我吞噬）, the natural process of breaking down cellular components¹⁴.

 

"Given that the ER-Golgi network is often dismantled¹⁵ in malignant¹⁶ conditions and that UVRAG is intensively involved in different types of human cancers, this study gives us a new avenue to investigate anti-cancer agents that target UVRAG and/or the ER-Golgi pathway in cancer and other relevant diseases," Liang said.

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