Int J Med Sci 2020; 17(8):995-1005. doi:10.7150/ijms.42805 This issue

Review

Inhibitor of Differentiation 1 (Id1) in Cancer and Cancer Therapy

Zhengxiao Zhao1#, Zhiyuan Bo2#, Weiyi Gong3, Yong Guo1✉

1. Department of Oncology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, China.
2. The Second Department of Biliary Tract Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China
3. The Department of Integrative Medicine, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, PR China
#Zhengxiao Zhao and Zhiyuan Bo contributed equally to this work.

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Citation:
Zhao Z, Bo Z, Gong W, Guo Y. Inhibitor of Differentiation 1 (Id1) in Cancer and Cancer Therapy. Int J Med Sci 2020; 17(8):995-1005. doi:10.7150/ijms.42805. Available from https://www.medsci.org/v17p0995.htm

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Abstract

The inhibitor of DNA binding (Id) proteins are regulators of cell cycle and cell differentiation. Of all Id family proteins, Id1 is mostly linked to tumorigenesis, cellular senescence as well as cell proliferation and survival. Id1 is a stem cell-like gene more than a classical oncogene. Id1 is overexpressed in numerous types of cancers and exerts its promotion effect to these tumors through different pathways. Briefly, Id1 was found significantly correlated with EMT-related proteins, K-Ras signaling, EGFR signaling, BMP signaling, PI3K/Akt signaling, WNT and SHH signaling, c-Myc signaling, STAT3 signaling, RK1/2 MAPK/Egr1 pathway and TGF-β pathway, etc. Id1 has potent effect on facilitating tumorous angiogenesis and metastasis. Moreover, high expression of Id1 plays a facilitating role in the development of drug resistance, including chemoresistance, radiation resistance and resistance to drugs targeting angiogenesis. However, controversial results were also obtained. Overall, Id1 represent a promising target of anti-tumor therapeutics based on its potent promotion effect to cancer. Numerous drugs were found exerting their anti-tumor function through Id1-related signaling pathways, such as fucoidan, berberine, tetramethylpyrazine, crizotinib, cannabidiol and vinblastine.

Keywords: Id1, Cancer, Signaling pathway, Angiogenesis, Resistance, Target