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    • A Widely Expressed Free Immunoglobulin Κ Chain with a Unique Vκ4-1/Jκ3 Pattern Promotes Colon Cancer Invasion and Metastasis by Activating the Integrin Β1/fak Pathway

    Qianqian Wang,Dongyang Jiang, Qing Ye,Wenjing Zhou,Junfan Ma,Chong Wang,Zihan Geng,Ming Chu,Jie Zheng, Hongchengcheng Chen,Jing Huang,Hui Dai,Youhui Zhang,Zhanlong Shen,Ning Fu,Xiaoyan Qiu

    Cancer Letters（2022）

    Department of Immunology

    Cited 3|Views43
    Abstract
    Historically, immunoglobulin (Ig) has been known as an antibody and is expressed only in B lineage cells; importantly, Ig light chains are conjugated to heavy chains to form intact Igs. However, in this study, we found a free Igκ light chain with a unique Vκ4-1/Jκ3 rearrangement (Vκ4-1/Jκ3-FLC) that was widely expressed in different non-B lineages and was overexpressed in cancer cells. Further study indicated that Vκ4-1/Jκ3-FLC was hydrophobic, formed obvious insoluble deposits in the extracellular matrix (ECM) and existed in free form. Functional analyses demonstrated that Vκ4-1/Jκ3-FLC promoted the proliferation, migration and metastasis of colon cancer cells in vitro and in vivo. Mechanistically, Vκ4-1/Jκ3-FLC bound to integrin β1 and activated the FAK and Src pathways. More importantly, specific antibodies against the variable region of Vκ4-1/Jκ3-FLC significantly inhibited the growth of colon cancer tumors. Our findings suggested that Vκ4-1/Jκ3-FLC is a novel ECM protein and integrin β1 ligand and that it is involved in cancer progression and is a potential therapeutic target in cancer, particularly colon cancer.
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    Key words
    Free light chain,Integrin,FAK/Src,Colon cancer
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