The epithelial Na+ channel/degenerin (ENaC/DEG) superfamily, including the acid-sensing ion channels (ASICs), is characterized by a high degree of similarity in structure but highly diverse in physiological functions. These ion channels have been shown to be important in several physiological functions of normal epithelial cells, including salt homeostasis, fluid transportation and cell mobility. There is increasing evidence suggesting that ENaC/DEG channels are critically engaged in cancer cell biology, such as proliferation, migration, invasion and apoptosis, playing a role in tumor development and progression. In this review, we will discuss recent studies showing the role of ENaC and ASIC channels in epithelial cells and its relationship to the oncogenesis.

Esophageal cancer is an aggressive disease featured by early lymphatic and hematogenous dissemination, and is the sixth leading cause of cancer-related deaths worldwide. The proper formation of apicobasal polarity is essential for normal epithelium physiology and tissue homeostasis, while loss of polarity is a hallmark of cancer development including esophageal oncogenesis. In this review, we summarized the stages of esophageal cancer development associated with the loss or deregulation of epithelial cell apicobasal polarity. Loss of epithelial apicobasal polarity exerts an indispensable role in the initiation of esophageal oncogenesis, tumor progression, and the advancement of tumors from benign to malignant. In particular, we reviewed the involvement of several critical genes, including Lkb1, claudin-4, claudin-7, Par3, Lgl1, E-cadherin, and the Scnn1 gene family. Understanding the role of apicobasal regulators may lead to new paradigms for treatment of esophageal tumors, including improvement of prognostication, early diagnosis, and individually tailored therapeutic interventions in esophageal oncology.

Esophageal squamous cell carcinoma (ESCC) has been well characterized as a major histological type in China and occurred predominantly in the mountain rural region with poor economics. Nutritional deficiencies have been recognized as major risk for esophageal carcinogenesis in these rural regions. In the past decades, the rural economic status in China has improved apparently. However, the time trending for ESCC in rural regions has not been characterized. The present study was thus undertaken to determine the time trending for the ratio of rural and urban patients with ESCC in a single institute in northern China over the past 30 years (1985-2014). All the 66,515 ESCC patients in this study were derived from the esophageal and gastric cardia carcinoma databases of 500 thousands patients (1973-2015) established by Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital of Zhengzhou University in Henan, China. Of the ESCC patients, 50,313 patients had been recorded with detailed address. Based on the diagnosed time, these patients were divided into three groups with periods of 1985-1994, 1995-2004 and 2005-2014. The rural and urban regions were recognized based on the government administrative division of China. The rural region in China refers to the farmer village with hundreds to thousands population. Chi-Square test was used to analyze the different distributions of ESCC patients with a p-value of less than 0.05 as significant. The results demonstrated that more than 84% of the ESCC patients occurred in rural regions with an overall ratio of 5:1 for rural and urban regions (p < 0.0001). Moreover, over the past 30 years with three periods, the ratios for rural and urban regions were 5.4:1, 5.5:1 and 5.4:1, respectively. The present results also demonstrated that over the past 30 years with three periods, ESCC occurred predominantly in males with ratios for male and female as 1.5:1, 1.4:1 and 1.5:1, respectively in rural regions and 1.6:1, 1.6:1 and 1.8:1, respectively in urban regions. Interestingly, the mean age both in male and female in urban regions was slightly older than that in rural regions (urban vs. rural: 60.7±9.86 vs. 59.8±9.38 in male and 62.2±9.57 vs. 60.6±9.47 in female, respectively). The present study demonstrated that ESCC remains the major healthy burden in rural regions in China. Considering the relative low socioeconomic status in China, the prevention and control of ESCC should be enhanced in rural regions in terms of more control programs, medical and education resources. [Supported by National High-Tech Research and Development Program of China (SQ2015AA0202183), Project for Characteristic and Advantage Discipline of Henan Province (20151208)] Note: This abstract was not presented at the meeting. Citation Format: Shou Jia Hu, Hai Jun Yang, Neng Chao Wang, Xiu Min Li, Shuang Lv, Qi De Bao, Wen Bin Yue, Hui Meng, Dan Feng Du, Xue Min Li, Fu You Zhou, Jian Li, Li Dong Wang. Time trending for the ratio of rural and urban patients with esophageal squamous cell carcinoma in a single institute in northern China over the past 30 years [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 264. doi:10.1158/1538-7445.AM2017-264