Fukumori Tomoharu, Kanayama Hiro-Omi, Raz Avraham
Department of Urology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
Drug Resist Updat. 2007 Jun;10(3):101-8. doi: 10.1016/j.drup.2007.04.001. Epub 2007 Jun 4.
The galectins comprise a family of 14 members of beta-galactoside-binding proteins, characterized by their affinity for beta-galactosides and by a conserved sequence in the carbohydrate recognition domain that bind to the carbohydrate portion of cell surface glycoproteins or glycolipids. Galectin-3, a 31kDa gene product, is a multifunctional oncogenic protein which regulates cell growth, cell adhesion, cell proliferation, angiogenesis, and apoptosis. Recent studies have revealed that galectin-3 demonstrates anti-apoptotic effects which contribute to cell survival in several types of cancer cells. Intracellular galectin-3 in particular, which contains the NWGR anti-death motif of the Bcl-2 family, inhibits cell apoptosis induced by chemotherapeutic agent such as cisplatin and etoposide in some types of cancer cells. We have also reported that nuclear export of phosphorylated galectin-3 regulates its anti-apoptotic activity in response to chemotherapeutic drugs. Here, we will describe the role of galectin-3 as an anti-apoptotic factor in response to chemotherapeutic drugs and will discuss recent data on its molecular mechanism that contribute to drug resistance. We suggest that targeting galectin-3 could improve the efficacy of anticancer drug chemotherapy in several types of cancer.
半乳糖凝集素是一个由14个β-半乳糖苷结合蛋白成员组成的家族,其特点是对β-半乳糖苷具有亲和力,且在碳水化合物识别结构域中有一个保守序列,该序列可与细胞表面糖蛋白或糖脂的碳水化合物部分结合。半乳糖凝集素-3是一种31kDa的基因产物,是一种多功能致癌蛋白,可调节细胞生长、细胞黏附、细胞增殖、血管生成和细胞凋亡。最近的研究表明,半乳糖凝集素-3具有抗凋亡作用,有助于几种癌细胞的存活。特别是细胞内的半乳糖凝集素-3,它含有Bcl-2家族的NWGR抗死亡基序,可抑制某些类型癌细胞中顺铂和依托泊苷等化疗药物诱导的细胞凋亡。我们还报道了磷酸化半乳糖凝集素-3的核输出调节其对化疗药物的抗凋亡活性。在此,我们将描述半乳糖凝集素-3作为抗凋亡因子在应对化疗药物中的作用,并讨论其导致耐药性的分子机制的最新数据。我们认为,靶向半乳糖凝集素-3可以提高几种癌症的抗癌药物化疗疗效。