脂肪酸合成酶在肿瘤细胞中的作用

Role of fatty acid synthase in tumor cells

脂肪酸合成酶(fatty acid synthase,FASN)是重要的生物合成酶,是肿瘤脂质生成的一种关键酶,在催化脂肪酸合成的过程中发挥重要作用。FASN在许多肿瘤细胞中过表达而在相应的正常细胞中却不表达。有证据表明FASN是一个代谢性癌基因,在癌细胞中高表达,在肿瘤生长和存活中有重要的作用。最初发现的肿瘤细胞特殊代谢表型称Warburg效应。异常脂肪酸代谢与肿瘤生长、存活及侵袭相关,表明异常脂肪酸代谢为肿瘤生长提供了至关重要的物质和能量来源。FASN的过度表达与肿瘤的发生、演变、侵袭和预后有关。在多种肿瘤中观察到脂肪酸代谢途径中FASN的表达和活性提高,并且与不良预后密切相关,通过下调这些代谢酶的表达或利用特异性抑制剂抑制代谢酶活性,可抑制肿瘤的生长。研究发现,利用FASN抑制剂可明显抑制肿瘤的复发和转移。通过抑制FASN的酶活性而导致肿瘤细胞脂类饥饿,从而有效地抑制癌细胞增殖,促使其脱离恶性分裂周期并走向凋亡。正确认识FASN在肿瘤细胞中的表达调节,研究新的FASN抑制剂,可为肿瘤治疗提供新的方案。本文就脂肪酸合成酶及脂肪酸合成酶抑制剂在肿瘤细胞中的作用作一综述。

Fatty acid synthase(FASN)is an important biosynthetic enzyme,and it is a key enzyme in tumor lipid production.It plays an important role in catalyzing fatty acid synthesis.FASN is overexpressed in many tumor cells but not in the corresponding normal cells.Accumulating evidence suggests that FASN is a metabolic oncogene playing an important role in tumor growth and survival.The specific metabolic phenotype was originally known as the Warburg effect.Abnormal fatty acid metabolism is related to the survival and invasiveness of cancer cells indicating that abnormal fatty acid metabolism provides the crucial components and energy sources of cancer cells.Its overexpression is associated with the occurrence,evolution,invasion and prognosis of tumors.The expression and activity of FASN in the metabolic pathway of fatty acids were observed in various tumors,and it is closely related to poor prognosis.By down-regulating the expression of these metabolic enzymes or using specific inhibitors,inhibiting the activity of metabolic enzymes can inhibit tumor growth.It is found that FASN inhibitors inhibit tumor recurrence and metastasis.By inhibiting the enzyme activity of FASN,it leads to lipid starvation of tumor cells,thus effectively inhibiting the proliferation of cancer cells,so that it can break away from the vicious cycle and go to apoptosis.Understanding the regulatory mechanism of FASN expression may help developing novel FASN inhibitors and may provide new therapeutic moieties for neoplasms therapy.The role of FASN and FASN inhibitors in tumor cell,is reviewed in this paper.