Abstract
TIGAR is a p53 target gene that is known to protect cells from ROS-induced apoptosis by promoting the pentose phosphate pathway. The role of TIGAR in tumor cell invasion and metastasis remains elusive. Here we found that downregulation of TIGAR reduced the invasion and metastasis of NSCLC cells in vitro and in vivo. Immunohistochemical analysis of 72 NSCLC patients showed that TIGAR and Met protein expression was positively correlated with late stages of lung cancer. Besides, patients with high co-expression of TIGAR and Met presented a significantly worse survival. In addition, we found that Met signaling pathway is involved in TIGAR-induced invasion and metastasis. Our study indicates that TIGAR/Met pathway may be a novel target for NSCLC therapy. It is necessary to evaluate the expression of TIGAR before Met inhibitors are used for NSCLC treatment.
Highlights
Cancer statistics collected by the American Cancer Society show that lung and bronchogenic cancer are the leading causes of cancer-related deaths in the United States [1]
Upregulation of phosphate pathway (PPP) genes in metastatic lesions compared to primary tumors has been observed in circulating melanoma cells [6], metastatic renal cell carcinoma (RCC) [7] and breast cancer [8]
TP53-induced glycolysis and apoptosis regulator (TIGAR) promotes cancer cell motility and invasion in vitro To explore the role of TIGAR in lung cancer invasion and metastasis, we investigated the endogenous levels of TIGAR in five human NSCLC cell lines
Summary
Cancer statistics collected by the American Cancer Society show that lung and bronchogenic cancer are the leading causes of cancer-related deaths in the United States [1]. The trend of lung cancer mortality in China increased markedly and likely to continue to rise [2]. Frequent presence of lung cancer metastases significantly affects efficiency of conventional therapies and induces treatment failure and high mortality [3]. TP53-induced glycolysis and apoptosis regulator (TIGAR) decreases the level of fructose-2,6-bisphospahte(F-2,6-P2) and subsequently reduces the activity of phosphofructosekinase-1(PFK1). Since PFK1 is the key enzyme in the control of glycolysis, TIGAR leads to glycolysis inhibition and promotes pentose phosphate pathway (PPP) [4]. Tumor metastasis requires metabolic changes to adapt secondary microenvironment [5]. Upregulation of PPP genes in metastatic lesions compared to primary tumors has been observed in circulating melanoma cells [6], metastatic renal cell carcinoma (RCC) [7] and breast cancer [8].
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