Cytoplasmic c-ros oncogene 1 receptor tyrosine kinase expression may be associated with the development of human oral squamous cell carcinoma

Abstract

Abstract. The c-ros oncogene 1 receptor tyrosine kinase (ROS1) gene encodes a proto-oncogenic protein that has been demonstrated to be involved in the pathogenesis of several types of cancer. The present study aimed to analyze the expression of ROS1 in human oral squamous cell carcinomas (OSCCs), and investigate the association between its expression and the clinicopathological parameters of patients with OSCC. Paraffin-embedded OSCC tissues from 31 patients were obtained and the expression of ROS1 was analyzed by immunohistochemistry. The cellular location of ROS1 was determined by immunofluorescence in human oral cancer CAL-27 cells. The association of clinicopathological characteristics and survival rates with ROS1 expression were assessed. The results revealed that ROS1 was exclusively localized in the cytoplasm of the OSCC tissues (24/30, 80.0%), and in the cytoplasm of adjacent dysplastic epithelial tissues (2/15, 13.3%) (P<0.001). The moderate to strong expression of ROS1 in the cytoplasm was higher in OSCC tissues than in the normal epithelial tissues adjacent to the tumor (67.7 vs. 0%, P=0.001). The results of the Kaplan-Meier analysis and multivariate Cox regression analysis indicated that there was no association between the 5-year survival rate of patients and the cytoplasmic (P=0.28 and P=0.60, respectively) or nuclear expression (P=0.90 and P=0.31, respectively) of ROS1. These results suggest that the cytoplasmic expression level of ROS1 may be associated with the development of OSCC.

In Vivo Assessment of Skin Chemical Burns in Exposure to Vesicants and the Efficacy of an Antidote Formula in Different Pharmaceutical Forms. An Experimental Approach

“…At the molecular level, the activation of anti-c-ROS-1 and anti-PARP-1 antibodies' expression was found. The expression of the c-ROS-1 antibody, a member of the tyrosine kinase receptor family, is correlated with cell growth and proliferation, including tumour proliferation, and is associated with in vitro sensitivity to tyrosine kinase inhibitors [5,32]. It is a marker of various forms of cellular stress transmitted through the cytoplasm to the nucleus.…”

Mitochondrial ROS1 Increases Mitochondrial Fission and Respiration in Oral Squamous Cancer Carcinoma

“…Confocal images of COS7 cells overexpressing ROS1-myc also showed significant distribution of ROS1 to mitochondria (Icorr = 0.811; Figure 1 B). The fact that Cheng and colleagues reported higher expression of ROS1 in the cytoplasm of OSCC tissues than that in the adjacent dysplastic, epithelial tissues suggests that the subcellular localization of ROS1 may be involved in disease progression [ 13 ]. We next used biochemical fractionation of the highly invasive OSCC cell line OC3-IV2 to confirm the subcellular location of ROS1, revealing that ROS1 was indeed present in both the mitochondrial and cytosolic fractions ( Figure 1 C).…”

Current treatment and novel insights regarding ROS1‐targeted therapy in malignant tumors

“…The overexpression of ROS1 was initially discovered in neurological tumors, such as primary gliomas 22 and meningiomas. 23 Cheng et al 24 found that ROS1 gene expression in the cytoplasm was positively correlated with the development of oral squamous cell carcinoma (OSCC). It has been suggested that ROS1 can mediate the invasiveness of OSCC by enhancing mitochondrial bioactivity and increasing cellular ATP levels.…”

“…The overexpression of ROS1 was initially discovered in neurological tumors, such as primary gliomas 22 and meningiomas 23 . Cheng et al 24 . found that ROS1 gene expression in the cytoplasm was positively correlated with the development of oral squamous cell carcinoma (OSCC).…”