Dataset Information

ARTEMIN Promotes Oncogenicity and Resistance to 5-Fluorouracil in Colorectal Carcinoma by p44/42 MAPK Dependent Expression of CDH2.

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.

SUBMITTER: Zhuang QS

PROVIDER: S-EPMC8377398 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

ARTEMIN Promotes Oncogenicity and Resistance to 5-Fluorouracil in Colorectal Carcinoma by p44/42 MAPK Dependent Expression of CDH2.

Zhuang Qiu-Shi QS Sun Xin-Bao XB Chong Qing-Yun QY Banerjee Arindam A Zhang Min M Wu Zheng-Sheng ZS Zhu Tao T Pandey Vijay V Lobie Peter E PE

Frontiers in oncology 20210806

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 tum ...[more]

PMID: 34422665

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Project description:Angiotensin II (Ang II), acting via angiotensin type 1 receptors in the brain, activates the sympathetic nervous system in heart failure (HF). We reported recently that Ang II stimulates mitogen-activated protein kinase (MAPK) to upregulate brain angiotensin type 1 receptors in HF rats. In this study we tested the hypothesis that Ang II-activated MAPK signaling pathways contribute to sympathetic excitation in HF. Intracerebroventricular administration of PD98059 and UO126, 2 selective p44/42 MAPK inhibitors, induced significant decreases in mean arterial pressure, heart rate, and renal sympathetic nerve activity in HF rats, but had no effect on these variables in sham-operated rats. Pretreatment with losartan attenuated the effects of PD98059. Intracerebroventricular administration of the p38 MAPK inhibitor SB203580 and the c-Jun N-terminal kinase inhibitor SP600125 had no effect on mean arterial pressure, heart rate, or renal sympathetic nerve activity in HF. The phosphatidylinositol 3-kinase inhibitor LY294002 induced a small decrease in mean arterial pressure and heart rate but no change in renal sympathetic nerve activity. Immunofluorescent staining demonstrated increased p44/42 MAPK activity in neurons of the paraventricular nucleus of the hypothalamus of HF rats, colocalized with Fra-like activity (indicating chronic neuronal excitation). Intracerebroventricular PD98059 and UO126 reduced Fra-like activity in the paraventricular nucleus of the hypothalamus neurons in HF rats. In confirmatory acute studies, intracerebroventricular Ang II increased mean arterial pressure, heart rate, and renal sympathetic nerve activity in baroreceptor-denervated rats and Fra-like immunoreactivity in the paraventricular nucleus of the hypothalamus of neurally intact rats. Central administration of PD98059 markedly reduced these responses. These data demonstrate that intracellular p44/42 MAPK activity contributes to Ang II-induced neuronal excitation in the paraventricular nucleus of the hypothalamus and augmented sympathetic nerve activity in rats with HF.

Dataset Information

ARTEMIN Promotes Oncogenicity and Resistance to 5-Fluorouracil in Colorectal Carcinoma by p44/42 MAPK Dependent Expression of CDH2.

Publications

ARTEMIN Promotes Oncogenicity and Resistance to 5-Fluorouracil in Colorectal Carcinoma by p44/42 MAPK Dependent Expression of CDH2.

Similar Datasets

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