Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression
Abstract Epithelial-mesenchymal transition (EMT) and proliferation play important roles in epithelial cancer formation and progression, but what molecules and how they trigger EMT is largely unknown. Here we performed spatial transcriptomic and functional analyses on samples of multistage esophageal...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-12-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-023-01710-2 |
| _version_ | 1797388042055450624 |
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| author | Liping Chen Shihao Zhu Tianyuan Liu Xuan Zhao Tao Xiang Xiao Hu Chen Wu Dongxin Lin |
| author_facet | Liping Chen Shihao Zhu Tianyuan Liu Xuan Zhao Tao Xiang Xiao Hu Chen Wu Dongxin Lin |
| author_sort | Liping Chen |
| collection | DOAJ |
| description | Abstract Epithelial-mesenchymal transition (EMT) and proliferation play important roles in epithelial cancer formation and progression, but what molecules and how they trigger EMT is largely unknown. Here we performed spatial transcriptomic and functional analyses on samples of multistage esophageal squamous-cell carcinoma (ESCC) from mice and humans to decipher these critical issues. By investigating spatiotemporal gene expression patterns and cell–cell interactions, we demonstrated that the aberrant epithelial cell interaction via EFNB1-EPHB4 triggers EMT and cell cycle mediated by downstream SRC/ERK/AKT signaling. The aberrant epithelial cell interaction occurs within the basal layer at early precancerous lesions, which expands to the whole epithelial layer and strengthens along the cancer development and progression. Functional analysis revealed that the aberrant EFNB1-EPHB4 interaction is caused by overexpressed ΔNP63 due to TP53 mutation, the culprit in human ESCC tumorigenesis. Our results shed new light on the role of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in EMT and cell proliferation in epithelial cancer formation. |
| first_indexed | 2024-03-08T22:34:01Z |
| format | Article |
| id | doaj.art-0fbe51c7074b4719928d92ce8e1f0d3f |
| institution | Directory Open Access Journal |
| issn | 2059-3635 |
| language | English |
| last_indexed | 2024-03-08T22:34:01Z |
| publishDate | 2023-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj.art-0fbe51c7074b4719928d92ce8e1f0d3f2023-12-17T12:31:22ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352023-12-018111610.1038/s41392-023-01710-2Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progressionLiping Chen0Shihao Zhu1Tianyuan Liu2Xuan Zhao3Tao Xiang4Xiao Hu5Chen Wu6Dongxin Lin7Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeDepartment of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract Epithelial-mesenchymal transition (EMT) and proliferation play important roles in epithelial cancer formation and progression, but what molecules and how they trigger EMT is largely unknown. Here we performed spatial transcriptomic and functional analyses on samples of multistage esophageal squamous-cell carcinoma (ESCC) from mice and humans to decipher these critical issues. By investigating spatiotemporal gene expression patterns and cell–cell interactions, we demonstrated that the aberrant epithelial cell interaction via EFNB1-EPHB4 triggers EMT and cell cycle mediated by downstream SRC/ERK/AKT signaling. The aberrant epithelial cell interaction occurs within the basal layer at early precancerous lesions, which expands to the whole epithelial layer and strengthens along the cancer development and progression. Functional analysis revealed that the aberrant EFNB1-EPHB4 interaction is caused by overexpressed ΔNP63 due to TP53 mutation, the culprit in human ESCC tumorigenesis. Our results shed new light on the role of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in EMT and cell proliferation in epithelial cancer formation.https://doi.org/10.1038/s41392-023-01710-2 |
| spellingShingle | Liping Chen Shihao Zhu Tianyuan Liu Xuan Zhao Tao Xiang Xiao Hu Chen Wu Dongxin Lin Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression Signal Transduction and Targeted Therapy |
| title | Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression |
| title_full | Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression |
| title_fullStr | Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression |
| title_full_unstemmed | Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression |
| title_short | Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression |
| title_sort | aberrant epithelial cell interaction promotes esophageal squamous cell carcinoma development and progression |
| url | https://doi.org/10.1038/s41392-023-01710-2 |
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