1The Second Military Medical University, Shanghai 200433, China;2Huai’an Affiliated Hospital of Xuzhou Medical University, Huaian 223002, Jiangsu, China; 3Department of Clinical Nutrition/Gastrointestinal Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China; 4Department of Biochemistry and Molecular Biology College of Basic Medical Sciences Second Military Medical University, Shanghai 200433, China
Abstract： TKTL-1 is a member of human TKT gene family, and the genes of the TKT family consist of TKT, TKTL-1 and TKTL-2. In human body, pentose phosphate pathway contains two pathways: oxidation pathway and non-oxidation pathway, TKT plays a key role in non-oxidative pathway. It catalyzes the conversion of ketose into aldose in the body. After a series of reactions, it continuously generates 5-phosphorylated ribose and NAPDH which are the raw materials of antioxidant response and biosynthesis. The current study suggests that there is a close relationship between TKTL-1 and the occurrence, development and metastasis of tumors. Some studies found that TKTL-1 has a different activity from other TKTs and shows high expression in many tumors, while the expressions of TKT and TKTL-2 in malignant tumors have no obvious regularity or just small changes. In this paper, we divide the role of TKTL-1 in malignant tumors into four aspects. First and foremost, TKTL-1 can provide raw materials for tumors, work in coordination with the reprogramming of cancer metabolism and provide a material basis for the proliferation and metastasis of malignant tumors. In addition, the high expression of TKTL-1 can promote the metastasis of tumor to peripheral lymph nodes. What’s more, TKTL-1 is closely related to the immunosuppression and drug resistance of the tumor: it produces lactic acid by glycolysis, inhibiting the immune monitoring of T cells and NK cells; and the inhibition of oxygen free radical production by lactic acid will reduce the antitumor effect of sorafenib and other drugs. At present, numerous studies have shown that TKTL-1 is a potential tumor marker which has great significance on the diagnosis and prognosis of tumors. In terms of treatment, studies have shown that the TKTL-1 inhibitors can inhibit tumor growth and metastasis, so TKTL-1 may be a potential biotherapeutic target. Co-treatment of TKTL-1 inhibitors with other metabolic modulation therapies may further enhance the anti-tumor efficacy of TKTL-1.
2018, Vol. 5 
