In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 2938-2938
Abstract:
Background and aim: Our previous study showed that high expression of CD73 (ecto-5’-nucleotidase) was a poor prognostic biomarker in patients with colorectal cancer (CRC). However, the underlying mechanism is unclear. Metastasis and chemo-resistance are among the main causes for the poor outcomes of CRC. The aim of this study is to evaluate the role of CD73 in the metastasis and chemo-resistance in CRC. Methods: The expression levels of CD73 were detected using quantitative RT-PCR and Western blot in 9 CRC cell lines and 3 5-FU-resistant cell lines (HCT8-FR, HCT116-FR, and RKO-FR). CD73 was overexpressed via lentiviral vector system and silenced using specific small interference RNA (si-CD73) in HCT8 and RKO. We then performed migration, invasion and MTS assays and wound healing assessment to evaluate the function of CD73 in cell progression and chemo-resistance. We conducted Cignal Finder Reporter Array to assess the main downstream signaling pathways of CD73. Results: Increased expression of CD73 was found in all 3 5-FU-resistant cell lines. Inhibition of CD73 expression in HCT8 and RKO by si-CD73 attenuated the capacity of cell migration and invasion but increased the sensitivity to 5-FU. On the other hand, overexpression of CD73 in HCT8 and RKO increased the capacity for cell migration but decreased the sensitivity to 5-FU. CD73-induced migration and chemo-resistance was found to be associated with the activation of MAPK/ERK pathway. Conclusions: High expression of CD73 was found to be associated with the metastasis and resistance to 5-FU via the activation of MAPK/ERK signaling pathway. This finding provides a molecular basis for the role of CD73 in the progression of CRC, suggesting a novel target for the treatment of CRC. Citation Format: Xuan-hui Liu, Xian-rui Wu, Yu-feng Chen, Feng-wei Wang, Xiao-bin Zheng, Dan Xie, Bo Shen, Jian-ping Wang, Xiao-jian Wu, Ping Lan. Role of CD73 in promoting metastasis and resistance to 5-fluorouracil of colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2938.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2016-2938
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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