Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression

被引：27

作者：

Chen, Liping ^{[1
]}

Zhu, Shihao ^{[1
]}

Liu, Tianyuan ^{[1
]}

Zhao, Xuan ^{[1
]}

Xiang, Tao ^{[1
]}

Hu, Xiao ^{[1
]}

Wu, Chen ^{[1
,2
,3
,4
]}

Lin, Dongxin ^{[1
,2
,3
,5
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Dept Etiol & Carcinogenesis, Natl Canc Ctr, Natl Clin Res Ctr Canc,Canc Hosp, Beijing 100021, Peoples R China

[2] Chinese Acad Med Sci & Peking Union Med Coll, Key Lab Canc Genom Biol, Beijing 100021, Peoples R China

[3] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Nanjing 211166, Peoples R China

[4] Chinese Acad Med Sci, CAMS Oxford Inst, Beijing 100006, Peoples R China

[5] Sun Yat Sen Univ, Canc Ctr, State Key Lab Oncol South China, Guangzhou 510060, Peoples R China

来源：

SIGNAL TRANSDUCTION AND TARGETED THERAPY | 2023年 / 8卷 / 01期

基金：

中国国家自然科学基金;

关键词：

RECEPTOR TYROSINE KINASE; FOLLOW-UP; CANCER; EXPRESSION; EPHB4; ACTIVATION; PATHWAY; RISK; P63; MYC;

D O I：

10.1038/s41392-023-01710-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 Delta NP63 due to TP53 mutation, the culprit in human ESCC tumorigenesis. Our results shed new light on the role of TP53-TP63/Delta NP63-EFNB1-EPHB4 axis in EMT and cell proliferation in epithelial cancer formation.

引用

页数：16

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