Impairing Golgin-45 transcription factor activity unleashes malignant secretion in lung cancer

Chao Wu; Abhishek Kumar; Shike Wang; Weina Zhao; Yuanxin Xi; Jing Wang; Abhinav K. Jain; William K. Russell; Hou-fu Guo; Xiaochao Tan; Jonathan M. Kurie

doi:10.1172/JCI209670

¹Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

²Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 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 Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States of America

⁵Department of Biochemistry, University of Texas Medical Branch, Galveston, United States of America

⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, United States of America

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¹Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

²Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 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 Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States of America

⁵Department of Biochemistry, University of Texas Medical Branch, Galveston, United States of America

⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, United States of America

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¹Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

²Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 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 Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States of America

⁵Department of Biochemistry, University of Texas Medical Branch, Galveston, United States of America

⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, United States of America

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¹Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, United States of America

²Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 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 Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States of America

⁵Department of Biochemistry, University of Texas Medical Branch, Galveston, United States of America

⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, United States of America

Find articles by Zhao, W. in: 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 Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 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 Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States of America

⁵Department of Biochemistry, University of Texas Medical Branch, Galveston, United States of America

⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, United States of America

Find articles by Xi, Y. in: 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 Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 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 Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States of America

⁵Department of Biochemistry, University of Texas Medical Branch, Galveston, United States of America

⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, United States of America

Find articles by Wang, J. in: 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 Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 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 Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States of America

⁵Department of Biochemistry, University of Texas Medical Branch, Galveston, United States of America

⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, United States of America

Find articles by Jain, A. in: 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 Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 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 Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States of America

⁵Department of Biochemistry, University of Texas Medical Branch, Galveston, United States of America

⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, United States of America

Find articles by Russell, W. in: 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 Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 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 Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States of America

⁵Department of Biochemistry, University of Texas Medical Branch, Galveston, United States of America

⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, United States of America

Find articles by Guo, H. in: 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 Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 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 Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States of America

⁵Department of Biochemistry, University of Texas Medical Branch, Galveston, United States of America

⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, United States of America

Find articles by Tan, X. in: 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 Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, 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 Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States of America

⁵Department of Biochemistry, University of Texas Medical Branch, Galveston, United States of America

⁶Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, United States of America

Find articles by Kurie, J. in: PubMed | Google Scholar

J Clin Invest. https://doi.org/10.1172/JCI209670.
Copyright © 2026, Wu et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published October 22, 2026 - Version history

Golgin-45 (G45) is a coiled-coil protein that transits reversibly between the Golgi and nucleus. In the Golgi, G45 serves as a tether for effectors of a pro-tumorigenic secretory program, but its nuclear role remains unclear. Here, we report that, upon entering the nucleus, G45 functions as a basic leucine zipper transcription factor. From genomic mapping, RNA-sequencing, and functional validation studies, we identify G45-binding sites and show that nuclear G45 can function as a transcriptional activator or repressor, a versatility enabled by phase separation into nuclear bodies enriched in transcriptional co-regulators. In lung cancer models, Golgi-docking reinforces, whereas nuclear translocation opposes, pro-tumorigenic activity of G45. Nuclear G45 incorporates into dimeric transcription factors that silence pro-tumorigenic secreted cargos. Epigenetic events in lung cancer degrade nuclear G45 and sequester G45 in the Golgi, which unleashes malignant secretion. Thus, inter-organelle transitions govern a G45-dependent secretory axis that drives lung cancer progression.

Impairing Golgin-45 transcription factor activity unleashes malignant secretion in lung cancer

Chao Wu,¹ Abhishek Kumar,¹ Shike Wang,² Weina Zhao,¹ Yuanxin Xi,³ Jing Wang,³ Abhinav K. Jain,⁴ William K. Russell,⁵ Hou-fu Guo,⁶ Xiaochao Tan,² and Jonathan M. Kurie¹

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Impairing Golgin-45 transcription factor activity unleashes malignant secretion in lung cancer

Chao Wu,1 Abhishek Kumar,1 Shike Wang,2 Weina Zhao,1 Yuanxin Xi,3 Jing Wang,3 Abhinav K. Jain,4 William K. Russell,5 Hou-fu Guo,6 Xiaochao Tan,2 and Jonathan M. Kurie1

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Chao Wu,¹ Abhishek Kumar,¹ Shike Wang,² Weina Zhao,¹ Yuanxin Xi,³ Jing Wang,³ Abhinav K. Jain,⁴ William K. Russell,⁵ Hou-fu Guo,⁶ Xiaochao Tan,² and Jonathan M. Kurie¹