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Title: ARTEMIN Promotes Oncogenicity and Resistance to 5-Fluorouracil in Colorectal Carcinoma by p44/42 MAPK Dependent Expression of CDH2
Authors: Zhuang, Qiu-Shi
Sun, Xin-Bao
Chong, Qing-Yun 
Banerjee, Arindam 
Zhang, Min
Wu, Zheng-Sheng
Zhu, Tao
Pandey, Vijay
Lobie, Peter E. 
Keywords: ARTEMIN
colorectal carcinoma
P44/42 MAPK
Issue Date: 6-Aug-2021
Publisher: Frontiers Media S.A.
Citation: Zhuang, Qiu-Shi, Sun, Xin-Bao, Chong, Qing-Yun, Banerjee, Arindam, Zhang, Min, Wu, Zheng-Sheng, Zhu, Tao, Pandey, Vijay, Lobie, Peter E. (2021-08-06). ARTEMIN Promotes Oncogenicity and Resistance to 5-Fluorouracil in Colorectal Carcinoma by p44/42 MAPK Dependent Expression of CDH2. Frontiers in Oncology 11 : 712348. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: ARTEMIN (ARTN), one of the glial-cell derived neurotrophic factor family of ligands, has been reported to be associated with a number of human malignancies. In this study, the enhanced expression of ARTN in colorectal carcinoma (CRC) was observed; the expression of ARTN positively correlated with lymph node metastases and advanced tumor stages and predicted poor prognosis. Forced expression of ARTN in CRC cells enhanced oncogenic behavior, mesenchymal phenotype, stem cell-like properties and tumor growth and metastasis in a xenograft model. These functions were conversely inhibited by depletion of endogenous ARTN. Forced expression of ARTN reduced the sensitivity of CRC cells to 5-FU treatment; and 5-FU resistant CRC cells harbored enhanced expression of ARTN. The oncogenic functions of ARTN were demonstrated to be mediated by p44/42 MAP kinase dependent expression of CDH2 (CADHERIN 2, also known as N-CADHERIN). Inhibition of p44/42 MAP kinase activity or siRNA mediated depletion of endogenous CDH2 reduced the enhanced oncogenicity and chemoresistance consequent to forced expression of ARTN induced cell functions; and forced expression of CDH2 rescued the reduced mesenchymal properties and resistance to 5-FU after ARTN depletion. In conclusion, ARTN may be of prognostic and theranostic utility in CRC. © Copyright © 2021 Zhuang, Sun, Chong, Banerjee, Zhang, Wu, Zhu, Pandey and Lobie.
Source Title: Frontiers in Oncology
ISSN: 2234-943X
DOI: 10.3389/fonc.2021.712348
Rights: Attribution 4.0 International
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