Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity
Recent studies have revealed that chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) promotes tumor progression and modulates tumor immunity by regulating programmed death-ligand 1 stability; however, its intrinsic functions and regulatory mechanisms in clear c...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2021.2011673 |
| _version_ | 1818754886470205440 |
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| author | Hanfeng Wang Yang Fan Weihao Chen Zheng Lv Shengpan Wu Yundong Xuan Chenfeng Wang Yongliang Lu Tao Guo Donglai Shen Fan Zhang Qingbo Huang Yu Gao Hongzhao Li Xin Ma Baojun Wang Yan Huang Xu Zhang |
| author_facet | Hanfeng Wang Yang Fan Weihao Chen Zheng Lv Shengpan Wu Yundong Xuan Chenfeng Wang Yongliang Lu Tao Guo Donglai Shen Fan Zhang Qingbo Huang Yu Gao Hongzhao Li Xin Ma Baojun Wang Yan Huang Xu Zhang |
| author_sort | Hanfeng Wang |
| collection | DOAJ |
| description | Recent studies have revealed that chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) promotes tumor progression and modulates tumor immunity by regulating programmed death-ligand 1 stability; however, its intrinsic functions and regulatory mechanisms in clear cell renal cell carcinoma (ccRCC) remain poorly understood. Here, we show that CMTM6 is upregulated in ccRCC tissues and is strongly associated with advanced tumor grades, early metastases, and a worse prognosis. CMTM6 depletion significantly impaired the proliferation, migration, and invasion of ccRCC cells in vitro and in xenograft mouse models in vivo. In addition, targeting CMTM6 promotes anti-tumor immunity, represented by increased infiltration of CD4+ and CD8+ T cells in syngeneic graft mouse models. Further research revealed that loss of CMTM6 triggered aberrant activation of DNA damage response, resulting in micronucleus formation and G2/M checkpoint arrest, finally leading to cellular senescence with robust upregulation of numerous chemokines and cytokines. Our findings show for the first time the novel role of CMTM6 in maintaining cancer genome stability and facilitating tumor-mediated immunosuppression, linking DNA damage signaling to the secretion of inflammatory factors. Targeting CMTM6 may improve the treatment of patients with advanced ccRCC. |
| first_indexed | 2024-12-18T05:30:23Z |
| format | Article |
| id | doaj.art-ccc1fb7464204a32a146dd97c23f2856 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-18T05:30:23Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-ccc1fb7464204a32a146dd97c23f28562022-12-21T21:19:28ZengTaylor & Francis GroupOncoImmunology2162-402X2022-12-0111110.1080/2162402X.2021.20116732011673Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunityHanfeng Wang0Yang Fan1Weihao Chen2Zheng Lv3Shengpan Wu4Yundong Xuan5Chenfeng Wang6Yongliang Lu7Tao Guo8Donglai Shen9Fan Zhang10Qingbo Huang11Yu Gao12Hongzhao Li13Xin Ma14Baojun Wang15Yan Huang16Xu Zhang17The Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalNankai UniversityThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalMedical School of Chinese PLAThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalThe Third Medical Center of PLA General HospitalRecent studies have revealed that chemokine-like factor-like MARVEL transmembrane domain-containing family member 6 (CMTM6) promotes tumor progression and modulates tumor immunity by regulating programmed death-ligand 1 stability; however, its intrinsic functions and regulatory mechanisms in clear cell renal cell carcinoma (ccRCC) remain poorly understood. Here, we show that CMTM6 is upregulated in ccRCC tissues and is strongly associated with advanced tumor grades, early metastases, and a worse prognosis. CMTM6 depletion significantly impaired the proliferation, migration, and invasion of ccRCC cells in vitro and in xenograft mouse models in vivo. In addition, targeting CMTM6 promotes anti-tumor immunity, represented by increased infiltration of CD4+ and CD8+ T cells in syngeneic graft mouse models. Further research revealed that loss of CMTM6 triggered aberrant activation of DNA damage response, resulting in micronucleus formation and G2/M checkpoint arrest, finally leading to cellular senescence with robust upregulation of numerous chemokines and cytokines. Our findings show for the first time the novel role of CMTM6 in maintaining cancer genome stability and facilitating tumor-mediated immunosuppression, linking DNA damage signaling to the secretion of inflammatory factors. Targeting CMTM6 may improve the treatment of patients with advanced ccRCC.http://dx.doi.org/10.1080/2162402X.2021.2011673cmtm6dna damagecellular senescenceimmunityrenal cell carcinoma |
| spellingShingle | Hanfeng Wang Yang Fan Weihao Chen Zheng Lv Shengpan Wu Yundong Xuan Chenfeng Wang Yongliang Lu Tao Guo Donglai Shen Fan Zhang Qingbo Huang Yu Gao Hongzhao Li Xin Ma Baojun Wang Yan Huang Xu Zhang Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity OncoImmunology cmtm6 dna damage cellular senescence immunity renal cell carcinoma |
| title | Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity |
| title_full | Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity |
| title_fullStr | Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity |
| title_full_unstemmed | Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity |
| title_short | Loss of CMTM6 promotes DNA damage-induced cellular senescence and antitumor immunity |
| title_sort | loss of cmtm6 promotes dna damage induced cellular senescence and antitumor immunity |
| topic | cmtm6 dna damage cellular senescence immunity renal cell carcinoma |
| url | http://dx.doi.org/10.1080/2162402X.2021.2011673 |
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