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Prion Protein Family Contributes to Tumorigenesis via Multiple Pathways

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Infectious Agents Associated Cancers: Epidemiology and Molecular Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1018))

Abstract

A wealth of evidence suggests that proteins from prion protein (PrP) family contribute to tumorigenesis in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), breast cancer, glioblastoma, colorectal cancer, gastric cancer, melanoma, etc. It is well documented that PrP is a biomarker for PDAC, breast cancer, and gastric cancer. However, the underlying mechanisms remain unclear. The major reasons for cancer cell-caused patient death are metastasis and multiple drug resistance, both of which connect to physiological functions of PrP expressing in cancer cells. PrP enhances tumorigenesis by multiple pathways. For example, PrP existed as pro-PrP in most of the PDAC cell lines, thus increasing cancer cell motility by binding to cytoskeletal protein filamin A (FLNa). Using PDAC cell lines BxPC-3 and AsPC-1 as model system, we identified that dysfunction of glycosylphosphatidylinositol (GPI) anchor synthesis machinery resulted in the biogenesis of pro-PrP. In addition, in cancer cells without FLNa expression, pro-PrP can modify cytoskeleton structure by affecting cofilin/F-actin axis, thus influencing cancer cell movement. Besides pro-PrP, we showed that GPI-anchored unglycosylated PrP can elevate cell mobility by interacting with VEGFR2, thus stimulating cell migration under serum-free condition. Besides affecting cancer cell motility, overexpressed PrP or doppel (Dpl) in cancer cells has been shown to increase cell proliferation, multiple drug resistance, and angiogenesis, thus, proteins from PrP gene family by affecting important processes via multiple pathways for cancer cell growth exacerbating tumorigenesis.

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Acknowledgments

This work was supported by National Science Foundation of China (31670170), by Nature Science Foundation of Hubei Province (2015CFA087), and by State Key Laboratory of Virology (2015IOV005).

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Authors and Affiliations

  1. Department of the First Abdominal Surgery, Jiangxi Tumor Hospital, Nanchang, Jiangxi, 330029, People’s Republic of China

    Xiaowen Yang & Zhijun Cheng

  2. Department of Pathology, Zhongda Hospital, Southeast University, Nanjing, 210009, People’s Republic of China

    Lihua Zhang

  3. Wuhan Institute of Virology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 44 xiao hong shan zhong qu, Wuhan, Hubei Province, 430071, People’s Republic of China

    Guiru Wu & Run Shi

  4. State Key Laboratory of Virology, Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430071, People’s Republic of China

    Zhenxing Gao & Chaoyang Li

  5. Hubei Collaborative Innovation Center for Industrial Fermentation, Wuhan, Hubei, 430068, People’s Republic of China

    Chaoyang Li

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  1. Xiaowen Yang
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  2. Zhijun Cheng
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  3. Lihua Zhang
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  4. Guiru Wu
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  5. Run Shi
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  6. Zhenxing Gao
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  7. Chaoyang Li
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Corresponding author

Correspondence to Chaoyang Li .

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Editors and Affiliations

  1. Key Laboratory of Medical Molecular Virology (Ministries of Education and Health), School of Basic Medical Science Fudan University, Shanghai, China

    Qiliang Cai

  2. Key Laboratory of Medical Molecular Virology (Ministries of Education and Health), School of Basic Medical Science Fudan University, Shanghai, China

    Zhenghong Yuan

  3. State Key Laboratory of Virology, College of Life Science, Wuhan University, Wuhan, China

    Ke Lan

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Yang, X. et al. (2017). Prion Protein Family Contributes to Tumorigenesis via Multiple Pathways. In: Cai, Q., Yuan, Z., Lan, K. (eds) Infectious Agents Associated Cancers: Epidemiology and Molecular Biology. Advances in Experimental Medicine and Biology, vol 1018. Springer, Singapore. https://doi.org/10.1007/978-981-10-5765-6_13

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