YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway
Abstract Radiotherapy is an important strategy in the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). However, effectiveness of radiotherapy is still restricted by radioresistance. Herein, we aimed to understand the mechanisms underlying ESCC radioresistance, for which we looke...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-12-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06321-x |
| _version_ | 1797397763055419392 |
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| author | Chunyan Zheng Zhe Li Chuanxi Zhao Xiaoyang Yin Lei Feng Zhongtang Wang Chengxin Liu Baosheng Li |
| author_facet | Chunyan Zheng Zhe Li Chuanxi Zhao Xiaoyang Yin Lei Feng Zhongtang Wang Chengxin Liu Baosheng Li |
| author_sort | Chunyan Zheng |
| collection | DOAJ |
| description | Abstract Radiotherapy is an important strategy in the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). However, effectiveness of radiotherapy is still restricted by radioresistance. Herein, we aimed to understand the mechanisms underlying ESCC radioresistance, for which we looked into the potential role of YY1. YY1 was upregulated in radioresistant tissues and correlated with poor prognosis of patients with ESCC. YY1 depletion enhanced the radiosensitivity of ESCC in vitro and in vivo. Multi-group sequencing showed that downregulation of YY1 inhibited the transcriptional activity of Kinesin Family Member 3B (KIF3B), which further activated the Hippo signaling pathway by interacting with Integrin-beta1 (ITGB1). Once the Hippo pathway was activated, its main effector, Yes-associated protein 1 (YAP1), was phosphorylated in the cytoplasm and its expression reduced in the nucleus, thus enhancing the radiosensitivity by regulating its targeted genes. Our study provides new insights into the mechanisms underlying ESCC radioresistance and highlights the potential role of YY1 as a therapeutic target for ESCC. |
| first_indexed | 2024-03-09T01:14:50Z |
| format | Article |
| id | doaj.art-9a984369bd25496599fc9890cc717253 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-09T01:14:50Z |
| publishDate | 2023-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-9a984369bd25496599fc9890cc7172532023-12-10T12:33:27ZengNature Publishing GroupCell Death and Disease2041-48892023-12-01141211210.1038/s41419-023-06321-xYY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathwayChunyan Zheng0Zhe Li1Chuanxi Zhao2Xiaoyang Yin3Lei Feng4Zhongtang Wang5Chengxin Liu6Baosheng Li7Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Radiation Oncology, The Affiliated Hospital of Qingdao UniversityDepartment of Radiation Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesShandong First Medical University and Shandong Academy of Medical SciencesAbstract Radiotherapy is an important strategy in the comprehensive treatment of esophageal squamous cell carcinoma (ESCC). However, effectiveness of radiotherapy is still restricted by radioresistance. Herein, we aimed to understand the mechanisms underlying ESCC radioresistance, for which we looked into the potential role of YY1. YY1 was upregulated in radioresistant tissues and correlated with poor prognosis of patients with ESCC. YY1 depletion enhanced the radiosensitivity of ESCC in vitro and in vivo. Multi-group sequencing showed that downregulation of YY1 inhibited the transcriptional activity of Kinesin Family Member 3B (KIF3B), which further activated the Hippo signaling pathway by interacting with Integrin-beta1 (ITGB1). Once the Hippo pathway was activated, its main effector, Yes-associated protein 1 (YAP1), was phosphorylated in the cytoplasm and its expression reduced in the nucleus, thus enhancing the radiosensitivity by regulating its targeted genes. Our study provides new insights into the mechanisms underlying ESCC radioresistance and highlights the potential role of YY1 as a therapeutic target for ESCC.https://doi.org/10.1038/s41419-023-06321-x |
| spellingShingle | Chunyan Zheng Zhe Li Chuanxi Zhao Xiaoyang Yin Lei Feng Zhongtang Wang Chengxin Liu Baosheng Li YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway Cell Death and Disease |
| title | YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway |
| title_full | YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway |
| title_fullStr | YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway |
| title_full_unstemmed | YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway |
| title_short | YY1 modulates the radiosensitivity of esophageal squamous cell carcinoma through KIF3B-mediated Hippo signaling pathway |
| title_sort | yy1 modulates the radiosensitivity of esophageal squamous cell carcinoma through kif3b mediated hippo signaling pathway |
| url | https://doi.org/10.1038/s41419-023-06321-x |
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