Ahmadshah Farhat1, Gordon A Ferns2, Korosh Ashrafi3, Mohammad-Hassan Arjmand3,4. 1. Neonatal Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Brighton & Sussex Medical School, Division of Medical Education, Brighton, United Kingdom. 3. Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran. 4. Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Abstract
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.
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.
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