Enhanced nuclear translation is associated with proliferation and progression across multiple cancers
Sailan Zou,
Byung‐Wook Kim,
Yan Tian,
Geng Liu,
Jiawei Zhang,
Ricardo Zerda,
Zhuo Li,
Guixiang Zhang,
Xiao Du,
Weiqiang Lin,
Xiang Gao,
Wendong Huang,
Xianghui Fu
Affiliations
Sailan Zou
Division of Endocrinology and Metabolism State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University and Collaborative Innovation Center of Biotherapy Chengdu China
Byung‐Wook Kim
Department of Diabetes Complications and Metabolism Arthur Riggs Diabetes and Metabolism Research Institute Irell & Manella Graduate School of Biological Sciences Beckman Research Institute City of Hope National Medical Center Duarte USA
Yan Tian
Division of Endocrinology and Metabolism State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University and Collaborative Innovation Center of Biotherapy Chengdu China
Geng Liu
Division of Endocrinology and Metabolism State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University and Collaborative Innovation Center of Biotherapy Chengdu China
Jiawei Zhang
Department of Diabetes Complications and Metabolism Arthur Riggs Diabetes and Metabolism Research Institute Irell & Manella Graduate School of Biological Sciences Beckman Research Institute City of Hope National Medical Center Duarte USA
Ricardo Zerda
Electron Microscopy and Atomic Force Microscopy Core City of Hope National Medical Center Duarte USA
Zhuo Li
Electron Microscopy and Atomic Force Microscopy Core City of Hope National Medical Center Duarte USA
Guixiang Zhang
Division of Gastrointestinal Surgery Department of General Surgery and Gastric Cancer Center West China Hospital Sichuan University Chengdu China
Xiao Du
Division of Gastrointestinal Surgery Department of General Surgery and Gastric Cancer Center West China Hospital Sichuan University Chengdu China
Weiqiang Lin
Department of Nephrology The Fourth Affiliated Hospital International Institutes of Medicine School of Medicine Zhejiang University Zhejiang China
Xiang Gao
Department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer Center West China Hospital West China Medical School Sichuan University and Collaborative Innovation Center for Biotherapy Chengdu China
Wendong Huang
Department of Diabetes Complications and Metabolism Arthur Riggs Diabetes and Metabolism Research Institute Irell & Manella Graduate School of Biological Sciences Beckman Research Institute City of Hope National Medical Center Duarte USA
Xianghui Fu
Division of Endocrinology and Metabolism State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University and Collaborative Innovation Center of Biotherapy Chengdu China
Abstract Recent technological advances have re‐invigorated the interest in nuclear translation (NT), but the underlying mechanisms and functional implications of NT remain unknown. Here we show that NT is enhanced in malignant cancer cells and is associated with rapid cell growth. Nuclear ribopuromycylation analyses in a panel of diverse cell lines revealed that NT is scarce in normal immortalized cells, but is ubiquitous and robust in malignant cancer cells. Moreover, NT occurs in the nucleolus and requires normal nucleolar function. Intriguingly, NT is reduced by cellular stresses and anti‐tumor agents and positively correlates with cancer cell proliferation and growth. By using a modified puromycin‐associated nascent chain proteomics, we further identified numerous oncoproteins that are preferentially translated in the nucleus, such as transforming growth factor‐beta 2 (TGFB2) and nucleophosmin 1 (NMP1). Specific overexpression of TGFB2 and NMP1 messenger RNAs in the nucleus can increase their protein levels and promote tumorigenesis. These findings establish a previously unknown link between NT and malignancy and suggest that cancer cells might have adapted a mechanism of NT to support their need for rapid growth, which highlight the potential of NT in tumorigenesis and might also open up new possibilities for therapeutic targeting of cancer‐specific cellular functions.
