Advertisement
ResearchIn-Press PreviewCell biologyOncology Open Access | 10.1172/JCI176355
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Tan, X. in: JCI | PubMed | Google Scholar |
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Wang, S. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Xiao, G. in: JCI | PubMed | Google Scholar |
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Wu, C. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Liu, X. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Zhou, B. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Yu, J. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Duose, D. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Xi, Y. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Wang, J. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Gupta, K. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Pataer, A. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Roth, J. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Kim, M. in: JCI | PubMed | Google Scholar |
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Chen, F. in: JCI | PubMed | Google Scholar
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Creighton, C. in: JCI | PubMed | Google Scholar |
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Russell, W. in: JCI | PubMed | Google Scholar |
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
2Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, United States of America
3Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
4Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India
5Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, United States of America
6Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America
7Department of Medicine and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, United States of America
8Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, United States of America
Find articles by Kurie, J. in: JCI | PubMed | Google Scholar
Published April 25, 2024 - More info
Cancer cells exhibit heightened secretory states that drive tumor progression. Here, we identify a chromosome 3q amplicon that serves as a platform for secretory regulation in cancer. The 3q amplicon encodes multiple Golgi-resident proteins, including the scaffold Golgi integral membrane protein 4 (GOLIM4) and the ion channel ATPase Secretory Pathway Ca2+ Transporting 1 (ATP2C1). We show that GOLIM4 recruits ATP2C1 and Golgi phosphoprotein 3 (GOLPH3) to coordinate calcium-dependent cargo loading and Golgi membrane bending and vesicle scission. GOLIM4 depletion disrupts the protein complex, resulting in a secretory blockade that inhibits the progression of 3q-amplified malignancies. In addition to its role as a scaffold, GOLIM4 maintains intracellular manganese (Mn) homeostasis by binding excess Mn in the Golgi lumen, which initiates the routing of Mn-bound GOLIM4 to lysosomes for degradation. We show that Mn treatment inhibits the progression of multiple types of 3q-amplified malignancies by degrading GOLIM4, resulting in a secretory blockade that interrupts pro-survival autocrine loops and attenuates pro-metastatic processes in the tumor microenvironment. Potentially underlying the selective activity of Mn against 3q-amplified malignancies, ATP2C1 co-amplification increases Mn influx into the Golgi lumen, resulting in a more rapid degradation of GOLIM4. These findings show that functional cooperativity between co-amplified genes underlies heightened secretion and a targetable secretory addiction in 3q-amplified malignancies.