Upregulation of CD44v6 contributes to acquired chemoresistance via the modulation of autophagy in colon cancer SW480 cells

doi:10.1007/s13277-015-4755-6

科研成果详情

题名	Upregulation of CD44v6 contributes to acquired chemoresistance via the modulation of autophagy in colon cancer SW480 cells
作者	Lv, Lin; Liu, Hai-Guang; Dong, Si-Yang; Yang, Fan; Wang, Qing-Xuan; Guo, Gui-Long; Pan, Yi-Fei; Zhang, Xiao-Hua
发表日期	2016-07
发表期刊	TUMOR BIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	CD44v6 Colorectal cancer Chemoresistance Autophagy
其他关键词	COLORECTAL-CANCER ; DRUG-RESISTANCE ; NEOADJUVANT CHEMOTHERAPY ; PROTEIN EXPRESSION ; PROGNOSTIC IMPACT ; STEM-CELLS ; VARIANT 6 ; BECLIN 1 ; 5-FLUOROURACIL ; METASTASIS
摘要	The CD44 isoform containing variant exon v6 (CD44v6) plays an important role in the progression, metastasis, and prognosis of colorectal cancer (CRC). Recently, it was found that CD44v6 is involved in acquired drug resistance. This study aimed to investigate the molecular mechanism of CD44v6 in the resistance of CRC cells to chemotherapy. A stable CD44v6 overexpression model in SW480 cells was established via lentiviral transduction. The chemosensitivity of cells to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) was determined by cell counting kit (CCK)-8, lactate dehydrogenase (LDH) release, and colony formation assays. Immunohistochemical staining of CD44v6 was performed in human CRC tissues. The key components in cell apoptosis, drug efflux and metabolism, mismatch repair, autophagy, epithelial-mesenchymal transition (EMT), and the PI3K-Akt and MAPK-Ras-Erk1/2 pathways were assessed using flow cytometry, quantitative real-time polymerase chain reaction (PCR), and western blot assays. The CD44v6 overexpression cells showed a higher viability, a lower LDH release rate, and an increased clonogenicity than the control cells under drug treatment. Moreover, overexpression of CD44v6 resulted in enhanced autophagy flux, EMT, and phosphorylation of Akt and Erk in the presence of drugs. Furthermore, high CD44v6 expression in the primary tumor was closely associated with an early recurrence in CRC patients who underwent curative surgery and adjuvant chemotherapy. In conclusion, overexpression of CD44v6 contributes to chemoresistance in SW480 cells under cytotoxic stress via the modulation of autophagy, EMT, and activation of the PI3K-Akt and MAPK-Ras-Erk pathways.
资助项目	Science Foundation from the Health Bureau of Wenzhou City of Zhejiang, China [Y20140713]; First Affiliated Hospital of Wenzhou Medical University [FHY2014013]
出版者	SAGE PUBLICATIONS LTD
出版地	LONDON
ISSN	1010-4283
EISSN	1423-0380
卷号	37 期号:7 页码:8811-8824
DOI	10.1007/s13277-015-4755-6
页数	14
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:000382174500032
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	26747179
SCOPUSEID	2-s2.0-84953388910
通讯作者地址	[Zhang, Xiao-Hua]Department of Oncology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
Scopus学科分类	Cancer Research
引用统计	被引频次：49[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/19033
专题	附属第一医院
通讯作者	Zhang, Xiao-Hua
作者单位	Department of Oncology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
第一作者单位	附属第一医院
通讯作者单位	附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Lv, Lin,Liu, Hai-Guang,Dong, Si-Yang,et al. Upregulation of CD44v6 contributes to acquired chemoresistance via the modulation of autophagy in colon cancer SW480 cells[J]. TUMOR BIOLOGY,2016,37(7):8811-8824.
APA	Lv, Lin., Liu, Hai-Guang., Dong, Si-Yang., Yang, Fan., Wang, Qing-Xuan., ... & Zhang, Xiao-Hua. (2016). Upregulation of CD44v6 contributes to acquired chemoresistance via the modulation of autophagy in colon cancer SW480 cells. TUMOR BIOLOGY, 37(7), 8811-8824.
MLA	Lv, Lin,et al."Upregulation of CD44v6 contributes to acquired chemoresistance via the modulation of autophagy in colon cancer SW480 cells".TUMOR BIOLOGY 37.7(2016):8811-8824.