CLC number:
On-line Access: 2025-01-14
Received: 2023-12-10
Revision Accepted: 2024-06-17
Crosschecked: 2024-09-09
Cited: 0
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Yilin ZHU, Fanrong LIU, Lei LIU, Jinfu WANG, Fengyuan GAO, Lan YE, Honglei WU, Chengjun ZHOU, Guimei LIN, Xiaogang ZHAO, Peichao LI. Chronic exposure to hexavalent chromium induces esophageal tumorigenesis via activating the Notch signaling pathway[J]. Journal of Zhejiang University Science B, 2025, 26(1): 76-91.
@article{title="Chronic exposure to hexavalent chromium induces esophageal tumorigenesis via activating the Notch signaling pathway",
author="Yilin ZHU, Fanrong LIU, Lei LIU, Jinfu WANG, Fengyuan GAO, Lan YE, Honglei WU, Chengjun ZHOU, Guimei LIN, Xiaogang ZHAO, Peichao LI",
journal="Journal of Zhejiang University Science B",
volume="26",
number="1",
pages="76-91",
year="2025",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300896"
}
%0 Journal Article
%T Chronic exposure to hexavalent chromium induces esophageal tumorigenesis via activating the Notch signaling pathway
%A Yilin ZHU
%A Fanrong LIU
%A Lei LIU
%A Jinfu WANG
%A Fengyuan GAO
%A Lan YE
%A Honglei WU
%A Chengjun ZHOU
%A Guimei LIN
%A Xiaogang ZHAO
%A Peichao LI
%J Journal of Zhejiang University SCIENCE B
%V 26
%N 1
%P 76-91
%@ 1673-1581
%D 2025
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300896
TY - JOUR
T1 - Chronic exposure to hexavalent chromium induces esophageal tumorigenesis via activating the Notch signaling pathway
A1 - Yilin ZHU
A1 - Fanrong LIU
A1 - Lei LIU
A1 - Jinfu WANG
A1 - Fengyuan GAO
A1 - Lan YE
A1 - Honglei WU
A1 - Chengjun ZHOU
A1 - Guimei LIN
A1 - Xiaogang ZHAO
A1 - Peichao LI
J0 - Journal of Zhejiang University Science B
VL - 26
IS - 1
SP - 76
EP - 91
%@ 1673-1581
Y1 - 2025
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300896
Abstract: hexavalent chromium Cr(VI), as a well-established carcinogen, contributes to tumorigenesis for many human cancers, especially respiratory and digestive tumors. However, the potential function and relevant mechanism of Cr(VI) on the initiation of esophageal carcinogenesis are largely unknown. Here, immortalized human esophageal epithelial cells (HEECs) were induced to be malignantly transformed cells, termed HEEC-Cr(VI) cells, via chronic exposure to Cr(VI), which simulates the progress of esophageal tumorigenesis. In vitro and in vivo experiments demonstrated that HEEC-Cr(VI) cells obtain the ability of anchorage-independent growth, greater proliferative capacity, cancer stem cell properties, and the capacity to form subcutaneous xenografts in BALB/c nude mice when compared to their parental cells, HEECs. Additionally, HEEC-Cr(VI) cells exhibited weakened cell motility and enhanced cell adhesion. Interestingly, HEECs with acute exposure to Cr(VI) failed to display those malignant phenotypes of HEEC-Cr(VI) cells, suggesting that Cr(VI)-induced malignant transformation, but not Cr(VI) itself, is the cause for the tumor characteristics of HEEC-Cr(VI) cells. Mechanistically, chronic exposure to Cr(VI) induced abnormal activation of Notch signaling, which is crucial to maintaining the capacity for malignant proliferation and stemness of HEEC-Cr(VI) cells. As expected,N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycinet-butyl ester (DAPT), an inhibitor for the Notch pathway, drastically attenuated cancerous phenotypes of HEEC-Cr(VI) cells. In conclusion, our study clarified the molecular mechanism underlying Cr(VI)-induced esophageal tumorigenesis, which provides novel insights for further basic research and clinical therapeutic strategies about Cr(VI)-associated esophageal cancer.
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