A team of researchers at Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, reported May 19 online in PLOS Genetics, identified minor type IV collagens as an important microenvironmental regulator of lung cancer progression.
Graduate student XIAO Qian and JIANG Yan with their colleagues, supervised by Prof. GE Gaoxiang from SIBCB, discovered minor type IV collagens are essential to lung cancer development, via both cancer cell autonomous and non-autonomous mechanisms. The functions of minor type IV collagens can not be compensated by the major type IV collagen.
Microenvironments of cells, via cell-cell communication, cell-extracellular matrix (ECM) interaction and growth factors, retain the characteristics of cells, as well as their response to stimuli. Aberrant change in ECM remodeling is one of the hallmarks in cancer progression.
Type IV collagens are components of basement membrane essential for the maintenance of tissue integrity and proper function. Type IV collagens are named as major type (α1α1α2) or minor type (α3α4α5 and α5α5α6) to reflect the abundance and tissue distribution of these collagens. Taking advantage of genetic mouse models, the researchers comprehensively investigated the functions of minor type IV collagens in lung cancer development. Ablation of minor type IV collagens significantly impeded the development of lung cancer without affecting major type IV collagen expression. Epithelial minor type IV collagens support cancer cell proliferation, while endothelial minor type IV collagens are essential for efficient tumor angiogenesis. Mechanistically, the minor type IV collagens, but not the major type IV collagen, signal through non-integrin collagen receptor discoidin domain receptor-1 (DDR1) to activate ERK in lung cancer cells and endothelial cells. The study reveals that major and minor type IV collagens are functionally distinct from each other, despite they are highly similar in sequence and domain structure. The minor type IV collagens are functionally indispensible.
This work, entitled “Minor Type IV Collagen α5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1”, was published online in PLOS Genetics on May 19, 2015. It was supported by grants from the National Natural Science Foundation of China.
CONTACT:
GE Gaoxiang, Principal Investigator
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Shanghai 200031, China
Phone: 86-21-54921102;
E-mail: gxge@sibcb.ac.cn
Fig. Endothelial minor type IV collagens promote angiogenesis. (Image provided by Dr. GE Gaoxiang`s group)
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