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IGFBP2: integrative hub of developmental and oncogenic signaling network

Oncogene volume 39, pages 2243–2257 (2020)Cite this article

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Abstract

Insulin-like growth factor (IGF) binding protein 2 (IGFBP2) was discovered and identified as an IGF system regulator, controlling the distribution, function, and activity of IGFs in the pericellular space. IGFBP2 is a developmentally regulated gene that is highly expressed in embryonic and fetal tissues and markedly decreases after birth. Studies over the last decades have shown that in solid tumors, IGFBP2 is upregulated and promotes several key oncogenic processes, such as epithelial-to-mesenchymal transition, cellular migration, invasion, angiogenesis, stemness, transcriptional activation, and epigenetic programming via signaling that is often independent of IGFs. Growing evidence indicates that aberrant expression of IGFBP2 in cancer acts as a hub of an oncogenic network, integrating multiple cancer signaling pathways and serving as a potential therapeutic target for cancer treatment.

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Fig. 1: Domain organization of human IGFBP2 protein.
Fig. 2: Diagram of IGFBP2 functions in embryogenesis and tumorigenesis.
Fig. 3: Schematic diagram of the oncogenic network governed by IGFBP2.
Fig. 4: Mode of signal transduction of IGFBP2 in tumorigenesis.

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Acknowledgements

We would like to thank all of the investigators who have contributed to the study of IGFBP2 in cancer that inspired this review article. This work was supported in part by the NCI Cancer Center Support Grant to the Comprehensive Cancer Center of Wake Forest University Health Sciences (P30CA012197). WZ is supported by the Hanes and Willis Professorship in Cancer and a Fellowship from the National Foundation for Cancer Research. XY and TL are supported by the National Natural Science Foundation of China (No. 81872063).

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Authors and Affiliations

  1. Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC, USA

    Tao Li, M. Elizabeth Forbes & Wei Zhang

  2. Tianjin Medical University General Hospital, Tianjin, China

    Tao Li, Jiabo Li & Xuejun Yang

  3. Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China

    Tao Li, Jiabo Li & Xuejun Yang

  4. Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Gregory N. Fuller

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  1. Tao Li
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Li, T., Forbes, M.E., Fuller, G.N. et al. IGFBP2: integrative hub of developmental and oncogenic signaling network. Oncogene 39, 2243–2257 (2020). https://doi.org/10.1038/s41388-020-1154-2

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