SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7
Abstract Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-02-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-04624-z |
| _version_ | 1828751379455279104 |
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| author | Zi-Mu Zhang Hai-Bo Cao Zhi-Heng Li Ran Zhuo Yan-Fang Tao Xiao-Lu Li Gen Li Xin-Mei Liao Fang Fang Yi Xie Di Wu Hai-Rong Wang Jian-Wei Wang Yan-Ling Chen Juan-Juan Yu Si-Qi Jia Ran-Dong Yang Xin-Yi Guo Yang Yang Chen-Xi Feng Yun-Yun Xu Guang-Hui Qian Jian Pan |
| author_facet | Zi-Mu Zhang Hai-Bo Cao Zhi-Heng Li Ran Zhuo Yan-Fang Tao Xiao-Lu Li Gen Li Xin-Mei Liao Fang Fang Yi Xie Di Wu Hai-Rong Wang Jian-Wei Wang Yan-Ling Chen Juan-Juan Yu Si-Qi Jia Ran-Dong Yang Xin-Yi Guo Yang Yang Chen-Xi Feng Yun-Yun Xu Guang-Hui Qian Jian Pan |
| author_sort | Zi-Mu Zhang |
| collection | DOAJ |
| description | Abstract Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling. |
| first_indexed | 2024-12-10T20:52:25Z |
| format | Article |
| id | doaj.art-ce19db75a6184127a7f08e5cbb461c61 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-10T20:52:25Z |
| publishDate | 2022-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-ce19db75a6184127a7f08e5cbb461c612022-12-22T01:34:03ZengNature Publishing GroupCell Death and Disease2041-48892022-02-0113211110.1038/s41419-022-04624-zSAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7Zi-Mu Zhang0Hai-Bo Cao1Zhi-Heng Li2Ran Zhuo3Yan-Fang Tao4Xiao-Lu Li5Gen Li6Xin-Mei Liao7Fang Fang8Yi Xie9Di Wu10Hai-Rong Wang11Jian-Wei Wang12Yan-Ling Chen13Juan-Juan Yu14Si-Qi Jia15Ran-Dong Yang16Xin-Yi Guo17Yang Yang18Chen-Xi Feng19Yun-Yun Xu20Guang-Hui Qian21Jian Pan22Institute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversitySchool of Electronic Information and Electrical Engineering, Shanghai Jiao Tong UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityMedical College of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityAbstract Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.https://doi.org/10.1038/s41419-022-04624-z |
| spellingShingle | Zi-Mu Zhang Hai-Bo Cao Zhi-Heng Li Ran Zhuo Yan-Fang Tao Xiao-Lu Li Gen Li Xin-Mei Liao Fang Fang Yi Xie Di Wu Hai-Rong Wang Jian-Wei Wang Yan-Ling Chen Juan-Juan Yu Si-Qi Jia Ran-Dong Yang Xin-Yi Guo Yang Yang Chen-Xi Feng Yun-Yun Xu Guang-Hui Qian Jian Pan SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7 Cell Death and Disease |
| title | SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7 |
| title_full | SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7 |
| title_fullStr | SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7 |
| title_full_unstemmed | SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7 |
| title_short | SAPCD2 promotes neuroblastoma progression by altering the subcellular distribution of E2F7 |
| title_sort | sapcd2 promotes neuroblastoma progression by altering the subcellular distribution of e2f7 |
| url | https://doi.org/10.1038/s41419-022-04624-z |
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