USC scientists ID protein that regulates cellular trafficking, potential for anti-cancer therapy

LOS ANGELES — Molecular microbiologists at the University of Southern California (USC) have uncovered intricate regulatory mechanisms 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 mechanism that coordinates two distinct intracellular processes that are critical to cellular homeostasis and disease development," said Chengyu Liang, M.D., Ph.D., a member of the USC Norris Comprehensive Cancer Center and principal investigator of the study.

The endoplasmic reticulum (ER) and Golgi apparatus are cellular organelles in eurkaryotic organisms where proteins are synthesized and packaged for secretion through the body. The trafficking of proteins between the ER and Golgi must be tightly modulated 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 transport and a new mechanistic connection between the physiological trafficking and the autophagic transportation of cellular material."

The researchers discovered that the UV irradiation resistance-associated gene protein (UVRAG), which has been implicated in the suppression of colon and breast cancer, coordinates trafficking of proteins between the ER and Golgi apparatus and also autophagy, the natural process of breaking down cellular components.

"Given that the ER-Golgi network is often dismantled in malignant 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.

USC co-authors include Duojiao Ni, Binyun Ma, Joo-Hyung Lee, Tian Zhang, Irene Ghozalli, Sara Dolatshahi Pirooz, Zhen Zhao, Soohwan Oh, Arlet Minassian and Pinghui Feng. The research was supported by the American Cancer Society (RSG-11-121-01-CCG) and National Institutes of Health (grants R01 CA140964, R21 CA161436 and U19AI083025).

Article cited: He, S., Ni, D., Ma, B., Lee, J.H., Zhang, T., Ghozalli, I. … & Liang, C. (2013). PI(3)P-bound UVRAG coordinates Golgi–ER retrograde and Atg9 transport by differential interactions with the ER tether and the Beclin 1 complex. Nature Cell Biology. Published online Sept. 22, 2013; doi:10.1038/ncb2848

USC Norris Comprehensive Cancer Center has been leading the fight to make cancer a disease of the past. As one of the eight original comprehensive cancer centers in the United States, its mission is to treat and prevent cancer by advancing and integrating education, research, and personalized patient care. For 40 years, USC Norris has been revolutionizing cancer research with innovative surgical techniques and novel cancer treatments. The cancer center's breakthroughs and discoveries in the field of epigenetics have led the way to a greater understanding of the underlying causes of cancer and new methods of prevention, detection, and treatment. With a multidisciplinary team of more than 250 dedicated scientists and physicians, USC Norris Comprehensive Cancer Center offers patients hope in the battle against cancer.

Keck Medicine of USC is the University of Southern California's medical enterprise, one of only two university-owned academic medical centers in the Los Angeles area. Encompassing academic, research and clinical entities, it consists of the Keck School of Medicine of USC, one of the top medical schools in Southern California; the renowned USC Norris Comprehensive Cancer Center, one of the first comprehensive cancer centers established in the United States; the USC Care faculty practice; the Keck Medical Center of USC, which includes two acute care hospitals: 411-bed Keck Hospital of USC and 60-bed USC Norris Cancer Hospital; and USC Verdugo Hills Hospital, a 158-bed community hospital. It also includes outpatient facilities in Beverly Hills, downtown Los Angeles, La Cañada Flintridge, Pasadena, and the USC University Park campus. USC faculty physicians and Keck School of Medicine departments also have practices throughout Los Angeles, Orange and Riverside counties.