Translational Oncology (Sep 2019)
Telomere Maintenance-Associated PML Is a Potential Specific Therapeutic Target of Human Colorectal Cancer
- Peng Gong,
- Hua Wang,
- Jingsong Zhang,
- Yudong Fu,
- Zhengmao Zhu,
- Jinmiao Wang,
- Yu Yin,
- Haiying Wang,
- Zhongcheng Zhou,
- Jiao Yang,
- Linlin Liu,
- Mo Gou,
- Ming Zeng,
- Jinghua Yuan,
- Feng Wang,
- Xinghua Pan,
- Rong Xiang,
- Sherman M. Weissman,
- Feng Qi,
- Lin Liu
Affiliations
- Peng Gong
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China
- Hua Wang
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China
- Jingsong Zhang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Yudong Fu
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China
- Zhengmao Zhu
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China
- Jinmiao Wang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China
- Yu Yin
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China
- Haiying Wang
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China
- Zhongcheng Zhou
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China
- Jiao Yang
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China
- Linlin Liu
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China
- Mo Gou
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China
- Ming Zeng
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China
- Jinghua Yuan
- Department of Genetics, Tianjin Medical University, Tianjin, 300070, China
- Feng Wang
- Department of Genetics, Tianjin Medical University, Tianjin, 300070, China
- Xinghua Pan
- Department of Genetics, Yale School of Medicine, New Haven, CT, 06520, USA
- Rong Xiang
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy
- Sherman M. Weissman
- Department of Genetics, Yale School of Medicine, New Haven, CT, 06520, USA
- Feng Qi
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, China; Address all correspondence to: Feng Qi, Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China. or Lin Liu, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, China.
- Lin Liu
- State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, 300071, China; Address all correspondence to: Feng Qi, Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China. or Lin Liu, Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin, China.
- Journal volume & issue
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Vol. 12,
no. 9
pp. 1164 – 1176
Abstract
Telomere length maintenance is essential for cell proliferation, which is particularly prominent in cancer. We validate that the primary colorectal tumors exhibit heterogeneous telomere lengths but mostly (90%) short telomeres relative to normal tissues. Intriguingly, relatively short telomeres are associated with tumor malignancy as indicated by poorly differentiated state, and these tumors contain more cancer stem-like cells (CSLCs) identified by several commonly used markers CD44, EPHB2 or LGR5. Moreover, promyelocytic leukemia (PML) and ALT-associated PML nuclear bodies (APBs) are frequently found in tumors with short telomeres and high proliferation. In contrast, distant normal tissues rarely or only minimally express PML. Inhibition of PML and APBs by an ATR inhibitor decreases proliferation of CSLCs and organoids, suggesting a potential therapeutic target to progressive colorectal tumors. Together, telomere maintenance underling tumor progression is connected with CSLCs.
