Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan.
Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
Int J Mol Sci. 2020 Dec 21;21(24):9751. doi: 10.3390/ijms21249751.
The lysyl oxidase (LOX) family members are secreted copper-dependent amine oxidases, comprised of five paralogues: LOX and LOX-like l-4 (LOXL1-4), which are characterized by catalytic activity contributing to the remodeling of the cross-linking of the structural extracellular matrix (ECM). ECM remodeling plays a key role in the angiogenesis surrounding tumors, whereby a corrupt tumor microenvironment (TME) takes shape. Primary liver cancer includes hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), ranked as the seventh most common cancer globally, with limited therapeutic options for advanced stages. In recent years, a growing body of evidence has revealed the key roles of LOX family members in the pathogenesis of liver cancer and the shaping of TME, indicating their notable potential as therapeutic targets. We herein review the clinical value and novel biological roles of LOX family members in tumor progression and the TME of liver cancers. In addition, we highlight recent insights into their mechanisms and their potential involvement in the development of target therapy for liver cancer.
赖氨酰氧化酶(LOX)家族成员是分泌的铜依赖性胺氧化酶,由五个同源物组成:LOX 和 LOX 样蛋白 1-4(LOXL1-4),它们的特征是具有催化活性,有助于结构细胞外基质(ECM)的交联重塑。ECM 重塑在肿瘤周围的血管生成中起着关键作用,从而形成腐败的肿瘤微环境(TME)。原发性肝癌包括肝细胞癌(HCC)和胆管癌(CCA),在全球范围内排名第七,晚期阶段的治疗选择有限。近年来,越来越多的证据揭示了 LOX 家族成员在肝癌发病机制和 TME 形成中的关键作用,表明它们作为治疗靶点具有显著的潜力。本文综述了 LOX 家族成员在肝癌肿瘤进展和 TME 中的临床价值和新的生物学作用。此外,我们还强调了它们的机制的最新见解及其在肝癌靶向治疗发展中的潜在作用。