Extracellular matrix remodeling facilitates obesity-associated cancer progression

Obesity is associated with leading causes of death, namely metabolic diseases and cancers. Obesity-associated metabolic dysfunction in adipose tissue (AT) contributes to cancer development by altering the tumor microenvironment; remodeling extracellular matrix (ECM) proteins is one of the crucial factors during this process. ECM remodeling in AT in obesity has an important role in cancer progression, particularly at the levels of metastatic growth and acquired chemoresistance of cancer cells; thus, developing therapeutics targeting dysregulation of ECM remodeling would be beneficial. Obesity, a global public health concern, is an important risk factor for metabolic diseases and several cancers. Fibro-inflammation in adipose tissues (ATs) is tightly associated with the pathologies of obesity; excessive or uncontrolled extracellular matrix (ECM) production in AT has a crucial role in this pathogenesis. The ECM is a critical and functional component of various tissues, providing a mechanical and chemical network of proteins that controls cell survival, development, and tissue repair. The ECM is tightly regulated and dynamically remodeled; this is an important factor for AT expansion and can result in modifications to the physical shape and biological function of AT. Here, we focus on ECM remodeling in AT and how it affects obesity-related cancer progression. Obesity, a global public health concern, is an important risk factor for metabolic diseases and several cancers. Fibro-inflammation in adipose tissues (ATs) is tightly associated with the pathologies of obesity; excessive or uncontrolled extracellular matrix (ECM) production in AT has a crucial role in this pathogenesis. The ECM is a critical and functional component of various tissues, providing a mechanical and chemical network of proteins that controls cell survival, development, and tissue repair. The ECM is tightly regulated and dynamically remodeled; this is an important factor for AT expansion and can result in modifications to the physical shape and biological function of AT. Here, we focus on ECM remodeling in AT and how it affects obesity-related cancer progression. structural protein that comprises most of the ECM, including in connective tissues. At least 28 types of human collagen have been characterized and categorized into groups according to their function and structure. representative type of collagen that contributes to the pathogenesis of many diseases, including cancers and metabolic syndrome. proteomic approach that aims to identify or quantify proteases, their inhibitors, and their substrates on a system-wide scale. derivative produced by the degradation of elastin during vascular wall remodeling, implicated in cardiovascular and fibrotic diseases. cleaved secretory protein product of COL6A3 (C5-domain) associated with the progression of cancers and insulin resistance in peripheral tissues. dimerized proteoglycan that binds to integrin, collagens, and HS. Several isoforms are produced by alternative splicing, two of which are the main forms in vertebrates. protein comprising various sulfated repeating disaccharide units. HS has an important role in various biological activities, including development, homeostasis, angiogenesis, cancer cell proliferation, tumor angiogenesis, and metastasis. enzyme that cleaves HS. natural nonsulfated glycosaminoglycan polysaccharide comprising linear repeating disaccharide units (D-glucuronic acid and N-acetyl-D-glucosamine). hormone and a member of the secretory lipocalin family, which affects not only innate immunity and apoptosis, but also insulin sensitivity, food intake, and glucose metabolism. copper-containing enzyme that oxidizes lysine residues in collagen, generating covalent cross-links, stabilizing the ECM structure. zinc-containing and calcium-dependent enzymes that restrict tissue remodeling by processing and degrading matrix proteins, such as collagens. approved combination chemotherapy regimen for the treatment of several cancers, including gastric and colorectal cancer. secreted protein, also known as secreted phosphoprotein 1 (SPP1), that regulates biomineralization, bone remodeling, and immune function. study of terminal amino acid sequences in proteins to understand proteolytic cascades and cleavage sites. family of primary endogenous inhibitor of matrix metalloproteinases (MMPs) comprising four members.