Abstract 5745: Study on telomere shelterin component TPP1 in esophageal squamous cell carcinoma

Abstract

Abstract Esophageal cancer (EC) is one of the most aggressive cancer and ranks the sixth leading cause of cancer-related mortality worldwide, approximately 70% of global esophageal carcinoma cases occur in China and esophageal squamous cell carcinoma (ESCC) is the most frequent histological subtype of EC. Lacking of reliable early diagnostic markers and efficient medical and surgical treatment approaches, the five-year survival rate of ESCC is only about 4.4%.Therefore exploration of the genetic basis and the affiliated molecular mechanisms in ESCC could be beneficial to improve the diagnosis, therapy, and prevention of this disease. As an important telomere binding protein, TPP1 protects the ends of telomeres and maintains the genomic stability and integrity of chromosomes in eukaryotes. Previous investigation discovered that TPP1 might play an important role in the carcinogenesis and progression of some cancers. However, whether and/or how TPP1 participates in ESCC remains unclear. Here TPP1 was studied in 65 ESCC patients’ specimens including tumor tissue, the adjacent tissue, and the peripheral blood leukocytes, also the ESCC cell lines were employed to further explore the molecular mechanisms of TPP1 involved in the tumorigenesis of ESCC. In this study, TPP1 mRNA and protein were measured in the ESCC tissue specimens, peripheral blood leukocytes and also in ESCC cell lines using real time RT-PCR and Western Blot. The results showed that TPP1 mRNA level was significantly higher in ESCC tumor tissues compared with the adjacent tissues (P<0.05); the same trend was observed in ESCC cells (Eca109, Kyse150) vs human esophageal epithelial cells (HET-1A), respectively. However, in peripheral blood leukocytes, the expression of TPP1 did not show any difference between the cancer patients and the healthy controls. Among the 65 ESCC patients, TPP1 protein expression in 46 patients was obvious higher in tumor tissues than that in the matched adjacent tissues, although there were 19 patients in exception. Moreover, the TPP1 expression was correlated with the lymph nodes metastasis and CYF2, which is one of the potential tumor markers for diagnosis of esophageal carcinoma. To further explore the potential biological function of TPP1 in ESCC, stably- transfecting shRNA-TPP1 (sh-TPP1) and shRNA-Negative Control (sh-NC) expression constructs in ESCC cell lines were performed to study TPP1’s roles in ESCC. The colongenic assay showed that depletion of TPP1 decreased ESCC cells proliferation and cell growth, and the wound healing experiment and cell invasion transwell chamber test demonstrated that down-regulation of TPP1 suppressed the cell migration and invasion capabilities in vitro. Taken together, our findings revealed that TPP1 might play crucial roles in the pathogenesis of ESCC and targeting TPP1 could be a valuable potential for ESCC early diagnosis, intervention and therapeutics. Note: This abstract was not presented at the meeting. Citation Format: Lihua Yao, Jiang Zou, Ru Sun, Jiajing Cai, Guangcheng Huang, Qiang Ma, Lei Xu, Mayong Fu, Xiaolan Guo. Study on telomere shelterin component TPP1 in esophageal squamous cell carcinoma [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 5745. doi:10.1158/1538-7445.AM2017-5745