期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.606149
关键词
immune synapse; dendritic cell therapy; T cell immunotherapy; cancer treatment; actin regulation
资金
- Creative Research Initiative Program through National Research Foundation (NRF) - Ministry of Science and ICT (MSIT) [2015R1A3A2066253]
- Bio and Medical Technology Development Program through National Research Foundation (NRF) - Ministry of Science and ICT (MSIT) [2020M3A9G3080281]
- Basic Science Program through National Research Foundation (NRF) - Ministry of Education [2019R1C1C1009570]
- National R&D Program for Cancer Control, Ministry for Health and Welfare [1911264]
- GIST Research Institute (GRI) IBBR grant - GIST in 2020, South Korea
- National Research Foundation of Korea [2019R1C1C1009570, 2020M3A9G3080281, 2015R1A3A2066253] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Transgelin-2, the only member of the transgelin family expressed in immune cells, plays a crucial role in stabilizing the actin cytoskeleton and influencing tumor development and infectious diseases.
Transgelin-2, a small actin-binding protein, is the only transgelin family member expressed in immune cells. In T and B lymphocytes, transgelin-2 is constitutively expressed, but in antigen-presenting cells, it is significantly upregulated upon lipopolysaccharide stimulation. Transgelin-2 acts as a molecular staple to stabilize the actin cytoskeleton, and it competes with cofilin to bind filamentous (F)-actin. This action may enable immune synapse stabilization during T-cell interaction with cognate antigen-presenting cells. Furthermore, transgelin-2 blocks Arp2/3 complex-nucleated actin branching, which is presumably related to small filopodia formation, enhanced phagocytic function, and antigen presentation. Overall, transgelin-2 is an essential part of the molecular armament required for host defense against neoplasms and infectious diseases. However, transgelin-2 acts as a double-edged sword, as its expression is also essential for a wide range of tumor development, including drug resistance and metastasis. Thus, targeting transgelin-2 can also have a therapeutic advantage for cancer treatment; selectively suppressing transgelin-2 expression may prevent multidrug resistance in cancer chemotherapy. Here, we review newly discovered molecular characteristics of transgelin-2 and discuss clinical applications for cancer and immunotherapy.
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