Review
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World J Immunol. Nov 27, 2014; 4(3): 174-184
Published online Nov 27, 2014. doi: 10.5411/wji.v4.i3.174
Recent advances of cluster of differentiation 74 in cancer
Yu-Huei Liu, Jung-Yaw Lin
Yu-Huei Liu, Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung 40402, Taiwan
Yu-Huei Liu, Graduate Institute of Integrated Medicine, China Medical University, Taichung 40402, Taiwan
Jung-Yaw Lin, Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan
Jung-Yaw Lin, Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 11051, Taiwan
Author contributions: Liu YH and Lin JY solely contributed to this paper.
Supported by National Science Council of Taiwan, No. NSC 98-2320-B-002-050-MY2 and No. NSC 102-2320-B-039-032-MY3
Correspondence to: Jung-Yaw Lin, PhD, Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Room 942, No.1 Jen-Ai Road, Taipei 11051, Taiwan. linjy@ntu.edu.tw
Telephone: +886-2-23123456-88206 Fax: +886-2-23954776
Received: March 8, 2014
Revised: June 3, 2014
Accepted: July 25, 2014
Published online: November 27, 2014
Processing time: 256 Days and 4.5 Hours
Abstract

Cluster of differentiation 74 (CD74) performs multiple roles in B cells, T cells, and antigen-presenting cells within the immune system; it also participates in major histocompatibility complex class II-restricted antigen presentation and inflammation. Recently, a role for CD74 in carcinogenesis has been described. CD74 promotes cell proliferation and motility and prevents cell death in a macrophage migration inhibitory factor-dependent manner. Its roles as an accessory signal receptor on the cell surface and the ability to interact with other signaling molecules make CD74 an attractive therapeutic target for the treatment of cancer. This review focuses on the original role of CD74 in the immune system and its emerging tumor-related functions. First, the structure of CD74 will be summarized. Second, the current understandings about the expression, cellular localization, molecular mechanisms and signaling pathways of CD74 in immunity and cancer will be reviewed. Third, the examples that suggest CD74 is a promising molecular therapeutic target are reviewed and discussed. Although the safety and efficacy of CD74-targeted strategies are under development, deeply understanding of the regulation of CD74 will hold promise for the use of CD74 as a therapeutic target and may develop the CD74-targeted therapeutic agents such as neutralized antibody and compounds.

Keywords: Cluster of differentiation 74; Invariant chain; Immune; Inflammation; Tumorigenesis; Cancer metastasis

Core tip: There are several structural and functional variants of cluster of differentiation 74 (CD74), each with their own expression pattern. Although this diversity may be required for normal homeostasis, it can lead to aberrant proliferation when dysregulated. This review focuses on the primary role of CD74 in the immune system and how the activity of this evolutionarily conserved molecule is subverted during tumorigenesis.