title: Paxillin is positively correlated with the clinicopathological factors of colorectal cancer, and knockdown of Paxillin improves sensitivity to cetuximab in colorectal cancer cells.
abstract: 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.
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Junling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Xiangzheng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Yucun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000068818:Cetuximab / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques / Q000379:methods*; D019073:HT29 Cells; D006801:Humans; D051419:Paxillin / Q000378:metabolism*; D011379:Prognosis; D016019:Survival Analysis
chemical_list: C496061:PXN protein, human; D051419:Paxillin; D000068818:Cetuximab