We further selleck chemicals Crizotinib tested P53 protein level and found that P53 increased slightly in CRNN overexpressed cells compared with vector control cells. It was reported that p53 could be activated by DNA damage in KYSE30 with mutant p53 as other ESCC cell line with wide-type p53 [38]. qRT-PCR results also indicated that p21 mRNA level increased in CRNN overexpressed cells. Taken together, we hypothesize that overexpression of CRNN could upregulate P53, and it subsequently increases P21 and Rb and inhibit G1/S transition. In the present study, the tumor suppressive function of CRNN has been clearly demonstrated, however, the molecular mechanism of CRNN in ESCC development remains unclear. CRNN has been reported to allow cells to tolerate normally lethal levels of deoxycholic acid and protect from the toxic effect of bile acid as a survival factor [39].

Further study identified CRNN as a potential component of epithelial immunity based on its strong signature of adaptive evolution on DNA sequence of a type that is commonly associated with a coevolutionary arms race with a pathogen [40]. Therefore, the expression of CRNN protein will presumably help maintain the barrier function in squamous epithelium in response to injury and function as a tumor suppressor [10]. In conclusion, we demonstrate that CRNN is a potential tumor suppressor in ESCC via arresting cell cycle progression at G1/S checkpoint by upregulating P21WAF1/CIP1 and Rb. A better understanding of the tumor suppressive role of CRNN will significantly improve our knowledge in the development of ESCC, and may lead to a more effective management of ESCC patients with the inactivation of CRNN.

Supporting Information Figure S1 IHC staining with CK4 and CK (pan) in CRNN overexpression cells and vector control cells. Original magnification: 200�� magnification. (JPG) Click here for additional data file.(122K, jpg) Funding Statement This work was supported by Grants from the National Natural Science Foundation of China (81272416, 81172338 and 81000863); the General Research Fund (HKU 7668/11M); Sun Yat-Sen University ��Hundred Talents Program�� (85000-3171311) and Sun Yat-sen University Young Talent Teachers Plan (11ykpy58). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Colorectal cancer accounts for approximately 10% of all new patient cases of cancer and Batimastat cancer-related deaths in the United States. In 2012, an estimated 143,460 new patient cases of colorectal cancer were diagnosed.1 Worldwide, the incidence of colorectal cancer is > 1,000,000 per year.2 The probability of developing colorectal cancer increases from 0.07% in the first four decades of life to 4.5% to 5% in the seventh decade of life.