Cancer Cells Enter an Adaptive Persistence to Survive Radiotherapy and Repopulate Tumor

Advanced Science - Tập 10 Số 8 - 2023
Yucui Zhao1, Tingting Lü2,3, Yanwei Song1, Yanqin Wen2, Zheng Deng1, Jiahui Fan2, Minghui Zhao1, Ruyi Zhao1, Yuntao Luo1, Jianzhu Xie1, Binjie Hu1, Haoran Sun1, Yiwei Wang1, Sijia He1, Yanping Gong1, Jin Cheng1, Xinjian Liu4, Yukui Zhang5, Jikun Li5, Chuan‐Yuan Li6, Yongyong Shi2,7, Qian Huang1
1Shanghai Key Laboratory for Pancreatic Diseases and Cancer Center Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 201620 China
2Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China
3Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310009 China
4Department of Biochemistry School of Medicine Sun Yat-sen University Shenzhen 518107 China
5Department of General Surgery Shanghai General Hospital Shanghai Jiao Tong University School of Medicine Shanghai 201620 China
6Department of Dermatology Duke University Medical Center Box 3135 Durham NC 27710 USA
7Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes) Qingdao University Qingdao 266003 China

Tóm tắt

AbstractRepopulation of residual tumor cells impedes curative radiotherapy, yet the mechanism is not fully understood. It is recently appreciated that cancer cells adopt a transient persistence to survive the stress of chemo‐ or targeted therapy and facilitate eventual relapse. Here, it is shown that cancer cells likewise enter a “radiation‐tolerant persister” (RTP) state to evade radiation pressure in vitro and in vivo. RTP cells are characterized by enlarged cell size with complex karyotype, activated type I interferon pathway and two gene patterns represented by CST3 and SNCG. RTP cells have the potential to regenerate progenies via viral budding‐like division, and type I interferon‐mediated antiviral signaling impaired progeny production. Depleting CST3 or SNCG does not attenuate the formation of RTP cells, but can suppress RTP cells budding with impaired tumor repopulation. Interestingly, progeny cells produced by RTP cells actively lose their aberrant chromosomal fragments and gradually recover back to a chromosomal constitution similar to their unirradiated parental cells. Collectively, this study reveals a novel mechanism of tumor repopulation, i.e., cancer cell populations employ a reversible radiation‐persistence by poly‐ and de‐polyploidization to survive radiotherapy and repopulate the tumor, providing a new therapeutic concept to improve outcome of patients receiving radiotherapy.

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Advanced Science

Tập 10 Số 8

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