转酮醇酶样蛋白-1与恶性肿瘤关系研究进展

Research advances of TKTL-1 in malignant tumor

TKTL-1基因是人类TKT基因家族中的成员之一。TKT家族的基因有TKT、TKTL-1、TKTL-2。在人体中磷酸戊糖途径分为氧化途径和非氧化途径,而转酮醇酶正是非氧化途径的关键酶。转酮醇酶能够催化体内的酮糖变成醛糖,再经多步反应不断生成5-磷酸核糖和NAPDH,从而为细胞抗氧化和生物合成等过程提供原料。目前的研究认为TKTL-1与恶性肿瘤的发生、发展和转移之间有着密切联系。研究发现TKTL-1具有不同于其他两种转酮醇酶的活性,TKTL-1在许多恶性肿瘤中都存在高表达的现象,而TKT和TKTL-2在各种恶性肿瘤中的表达没有明显的规律或者变化幅度较小。本文将TKTL-1在恶性肿瘤中的作用大体分为四个方面。首先TKTL-1可以为肿瘤提供原料并且协同肿瘤代谢重编程,为肿瘤的恶性增殖和转移提供物质基础。其次,TKTL-1的高表达能够促进肿瘤向周围淋巴结转移。另外,TKTL-1还与肿瘤的免疫抑制和耐药性有关:TKTL-1通过糖酵解产生乳酸,抑制T胞和NK细胞对肿瘤的免疫监测;通过乳酸抑制氧自由基生成,降低索拉菲尼等药物的抗肿瘤疗效。目前,许多研究表明TKTL-1是一个潜在的肿瘤标志物,对于肿瘤的诊断和预后,有着极大的意义。在治疗方面,研究显示抑制TKTL-1的表达可以抑制肿瘤的生长和转移,所以TKTL-1可能是一种潜在的生物治疗靶点。TKTL-1抑制剂与其他代谢调节治疗方法联合进行治疗或许可进一步增强抗肿瘤疗效。

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.