Background: Malignancy is a complex process resulting from different changes such as extracellular matrix (ECM) remodeling and stiffness. One of the important enzymes that contribute to ECM remodeling is lysyl oxidase (Lox) that is overexpressed in different types of human cancers. Because of the high prevalence and poor survival of gastrointestinal (GI) malignancies in this review, we discuss the association between Lox activity and the progression of GI cancers. Lox proteins are a group of extracellular enzymes that catalyzed the cross-linking of collagen and elastin, so they have important roles in the control of structure and homeostasis of ECM. Abnormal activation and expression of the Lox family of proteins lead to changes in the ECM toward increased rigidity and fibrosis. Stiffness of ECM can contribute to the pathogenesis of cancers. Summary: Dysregulation of Lox expression is a factor in both fibrotic diseases and cancer. ECM stiffness by Lox overactivity creates a physical barrier against intratumoral concentration of chemotherapeutic drugs and facilitates cancer inflammation, angiogenesis, and metastasis. Key Message: Because of the roles of Lox in GI cancers, development targeting Lox protein isotypes may be an appropriate strategy for treatment of GI cancers and improvement in survival of patients.
Gastrointest Tumors

中文翻译：

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赖氨酰氧化酶介导胃肠癌进展的机制

背景：恶性肿瘤是由细胞外基质 (ECM) 重塑和僵硬等不同变化引起的复杂过程。有助于 ECM 重塑的重要酶之一是在不同类型的人类癌症中过度表达的赖氨酰氧化酶 (Lox)。由于本综述中胃肠道 (GI) 恶性肿瘤的高患病率和较差的存活率，我们讨论了 Lox 活性与胃肠道癌症进展之间的关联。Lox蛋白是一组催化胶原蛋白和弹性蛋白交联的细胞外酶，因此它们在控制ECM的结构和稳态中具有重要作用。Lox 蛋白家族的异常激活和表达导致 ECM 发生变化，从而增加刚性和纤维化。ECM 的僵硬可促进癌症的发病机制。摘要： Lox 表达失调是纤维化疾病和癌症的一个因素。Lox 过度活动导致的 ECM 僵硬形成了对抗肿瘤内化疗药物浓度的物理屏障，并促进了癌症炎症、血管生成和转移。关键信息：由于 Lox 在 GI 癌症中的作用，针对 Lox 蛋白同种型的开发可能是治疗 GI 癌症和提高患者生存率的适当策略。
胃肠肿瘤