Targeting type I collagen for cancer treatment
Run Shi, Zhe Zhang, An-Kai Zhu, Xingxing Xiong, Jie Zhang, Jiang Xu, Man‐Sun Sy, Chaoyang Li
Abstract
Collagen is the most abundant protein in animals. Interactions between tumor cells and collagen influence every step of tumor development. Type I collagen is the main fibrillar collagen in the extracellular matrix and is frequently upregulated during tumorigenesis. The binding of type I collagen to its receptors on tumor cells promotes tumor cell proliferation, epithelial-mesenchymal transition and metastasis. Type I collagen also regulates the efficacy of tumor therapies, such as chemotherapy, radiotherapy and immunotherapy. Furthermore, type I collagen fragments are diagnostic markers of metastatic tumors and have prognostic value. Inhibition of type I collagen synthesis has been reported to have antitumor effects in animal models. However, collagen has also been shown to possess antitumor activity. Therefore, the roles that type I collagen plays in tumor biology are complex and tumor type-dependent. In this review, we discuss the expression and regulation of synthesis of type I collagen, as well as the role upregulated type I collagen plays in various stages of cancer progression. We also discuss the role of collagen in tumor therapy. Finally, we highlight several recent approaches targeting type I collagen for cancer treatment.