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学科主题临床医学
Paxillin is positively correlated with the clinicopathological factors of colorectal cancer, and knockdown of Paxillin improves sensitivity to cetuximab in colorectal cancer cells
Du, Chuang1; Wang, Xin1; Zhang, Junling1; Liu, Xiangzheng2; Zhu, Jing1; Liu, Yucun1
关键词Paxillin Colorectal Cancer P-erk Apoptosis Cetuximab Resistance Clinicopathological Factors
刊名ONCOLOGY REPORTS
2016
DOI10.3892/or.2015.4352
35期:1页:409-417
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]COLON-CANCER ; EPITHELIAL MORPHOGENESIS ; MOLECULAR-MECHANISMS ; MONOCLONAL-ANTIBODY ; ACQUIRED-RESISTANCE ; 1ST-LINE TREATMENT ; GROWTH ; AUTOPHAGY ; KRAS ; PHOSPHORYLATION
英文摘要

Paxillin (PXN) encodes a 68-kDa focal adhesion-associated protein and plays an important role in signal transduction, regulation of cell morphology, migration, proliferation and apoptosis. The aim of the present study was to evaluate the relationship between PXN and clinicopathological factors in colorectal cancer, the role of PXN in cetuximab resistance, and whether knockdown of PXN expression could improve the sensitivity to cetuximab in colorectal cancer cells. In the present study, immunohistochemical staining in 148 colorectal carcinoma and 126 normal adjacent tissues was performed, which showed that the positive rate of PXN was significantly higher in the colorectal adenocarcinoma samples than that in the normal colorectal mucosa samples (P<0.001). Moreover, PXN presence was also positively correlated with TNM stage (P=0.023), distant metastasis (P=0.014), recurrence (P=0.032) and reduced survival (P=0.004). In vitro, PXN expression was positively correlated with the proliferation rate in colorectal cells insensitive to cetuximab. Inhibition of PXN expression by PXN-siRNA clearly increased apoptosis by downregulating the phosphorylation of extracellular signal regulated kinase (p-Erk) level, and overexpression of PXN by PXN-cDNA decreased apoptosis by upregulating the p-Erk level. This suggests that overexpression of PXN could be one of the reasons for cetuximab resistance, and downregulation of PXN plays an important role in improving sensitivity to cetuximab by suppressing the activitation of p-Erk in colorectal cancer cells. Above all, knockdown of PXN could represent a rational therapeutic strategy for increasing the sensitivity or overcoming cetuximab-resistance in patients with colorectal cancer.

语种英语
WOS记录号WOS:000366072500049
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56717
专题北京大学第一临床医学院_普通外科
作者单位1.Peking Univ, Hosp 1, Dept Gen Surg, Beijing 100034, Peoples R China
2.Peking Univ, Hosp 1, Dept Thorac Surg, Beijing 100034, Peoples R China
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Du, Chuang,Wang, Xin,Zhang, Junling,et al. Paxillin is positively correlated with the clinicopathological factors of colorectal cancer, and knockdown of Paxillin improves sensitivity to cetuximab in colorectal cancer cells[J]. ONCOLOGY REPORTS,2016,35(1):409-417.
APA Du, Chuang,Wang, Xin,Zhang, Junling,Liu, Xiangzheng,Zhu, Jing,&Liu, Yucun.(2016).Paxillin is positively correlated with the clinicopathological factors of colorectal cancer, and knockdown of Paxillin improves sensitivity to cetuximab in colorectal cancer cells.ONCOLOGY REPORTS,35(1),409-417.
MLA Du, Chuang,et al."Paxillin is positively correlated with the clinicopathological factors of colorectal cancer, and knockdown of Paxillin improves sensitivity to cetuximab in colorectal cancer cells".ONCOLOGY REPORTS 35.1(2016):409-417.
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