Co-overexpression of cortactin and CRKII increases migration and invasive potential in oral squamous cell carcinoma

Abstract

Cortactin stimulates cell migration, invasion, and experimental metastasis. Overexpression of cortactin has been reported in several human cancers. CRK was originally identified as an oncogene product of v-CRK in a CT10 chicken retrovirus system. Overexpression of CRKII has been reported in several human cancers. CRKII regulates cell migration, morphogenesis, invasion, phagocytosis, and survival; however, the underlying mechanisms are not well understood. We evaluated the possibility of the combination of cortactin and CRKII as an appropriate molecular target for cancer gene therapy. The expression of cortactin and CRKII in 70 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens was determined immunohistochemically, and the correlation of cortactin and CRKII co-overexpression with clinicopathological factors was evaluated. Co-overexpression of cortactin and CRKII was detected in 31 of 70 oral squamous cell carcinomas, the frequency being significantly greater than in normal oral mucosa. In addition, cortactin and CRKII co-overexpression was more frequent in higher-grade cancers according to 3 the T classification, N classification, and invasive pattern. RNAi-mediated co-suppression of cortactin and CRKII expression reduced the migration and invasion potential of an oral squamous cell carcinoma cell line, OSC20. Downregulation of cortactin and CRKII expression also reduced the expression of vimentin, fibronectin, and N-cadherin. These results indicate that the co-overexpression of cortactin and CRKII may be tightly associated with an aggressive phenotype of oral squamous cell carcinoma. Therefore, we propose that the combination of cortactin and CRKII could be a potential molecular target of gene therapy by RNAi-targeting in oral squamous cell carcinoma. 4 1.IntroductionOral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck region and accounts for more than 90% of cancers of the oral cavity [1]. The primary therapeutic modality for OSCC is surgery. Although recent advances in surgical techniques and anticancer agents have improved tumor regression and survival for patients with OSCC, wide surgical resection of OSCC inevitably causes various oral dysfunctions. Therefore, new treatment strategies are urgently needed.The presence of neck lymph node metastasis is strongly related to a poor prognosis in squamous cell carcinoma of the head and neck [2][3][4]. Moreover, it has been reported that an alteration in the expression of adhesion-related molecules is associated with poor prognosis in OSCC patients [5][6][7][8].Chromosomal band 11q13 is a frequently amplified genomic segment in a large number of malignant neoplasms, and is thought of as a potential biomarker for diagnosis and prognosis [9,10]. In head and neck squamous cell carcinoma, this amplification is one of the most frequently observed genetic alterations [11][12][13][14][15][16][17][18][19][20] and is reportedly correlated with aggressive tumor growth [9,13,19], the presence of lymph node ...

Cortactin expression in a Norwegian cohort of human papilloma virus negative oral squamous cell carcinomas of the mobile tongue

“…This indicates that the expres-sion of cortactin might be related to OTSCC invasion. These observations are in line with previous studies where cortactin expression was associated with increased invasive ability of OSCC cells and node status [15,34,35]. For example, siRNAmediated knock-down of CTTN was associated with reduced invasion ability of OSCC cells with concomitant modulation of epithelial and decrease in mesenchymal phenotype markers [15,34].…”