Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1

Shu Yi Yin, Thomas Efferth, Feng Yin Jian, Yung Hsiang Chen, Chia I. Liu, Andrew H J Wang, Yet Ran Chen, Pei Wen Hsiao, Ning Sun Yang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Immunogenic cell death (ICD) of tumor cells occurs via various pathways that activate immune cell systems against cancer. Previous studies have demonstrated that shikonin (SK), a plant secondary metabolite, can confer strong pharmacological activities that activate ICD and strong immunogenicity of tumor cells. However, the exact hierarchical regulatory mechanisms including the molecular targets of SK-activated immunogenicity are still unknown. Here, the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was revealed to serve as a specific protein target for SK. This binding plays a key role in SK-stimulated ICD activity and the suppression of post-transcriptional mRNA processing, including nuclear export activity of newly synthesized mRNAs in mammary carcinoma cells in vitro. Moreover, it also mechanistically mediates the anti-metastatic effect of a tumor cell lysate (TCL) vaccine, which can be readily generated from SK-treated 4T1 tumor cells (SK-TCL), and the derived tumor-immunogenicity of SK-TCL-treated dendritic cells in vivo. Together, the identification of hnRNPA1 as the intracellular molecular target provides compelling pharmacology-based knowledge for the potential clinical use of SK-induced immunogenicity. In addition, SK may also serve as a potent suppressor that interferes with specific post-transcriptional activities, a mechanism which may be useful for exploitation in cancer therapeutics.

Original languageEnglish
Pages (from-to)43629-43653
Number of pages25
JournalOncotarget
Volume7
Issue number28
DOIs
Publication statusPublished - 2016

Fingerprint

Heterogeneous-Nuclear Ribonucleoproteins
Breast Neoplasms
Neoplasms
Cell Death
Pharmacology
Messenger RNA
Cell Nucleus Active Transport
shikonin
Dendritic Cells
Immune System
Vaccines

Keywords

  • Heterogeneous nuclear ribonucleoprotein A1
  • Immunogenic cell death
  • Shikonin
  • Tumor immunogenicity

ASJC Scopus subject areas

  • Oncology

Cite this

Yin, S. Y., Efferth, T., Jian, F. Y., Chen, Y. H., Liu, C. I., Wang, A. H. J., ... Yang, N. S. (2016). Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1. Oncotarget, 7(28), 43629-43653. https://doi.org/10.18632/oncotarget.9660

Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1. / Yin, Shu Yi; Efferth, Thomas; Jian, Feng Yin; Chen, Yung Hsiang; Liu, Chia I.; Wang, Andrew H J; Chen, Yet Ran; Hsiao, Pei Wen; Yang, Ning Sun.

In: Oncotarget, Vol. 7, No. 28, 2016, p. 43629-43653.

Research output: Contribution to journalArticle

Yin, SY, Efferth, T, Jian, FY, Chen, YH, Liu, CI, Wang, AHJ, Chen, YR, Hsiao, PW & Yang, NS 2016, 'Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1', Oncotarget, vol. 7, no. 28, pp. 43629-43653. https://doi.org/10.18632/oncotarget.9660
Yin, Shu Yi ; Efferth, Thomas ; Jian, Feng Yin ; Chen, Yung Hsiang ; Liu, Chia I. ; Wang, Andrew H J ; Chen, Yet Ran ; Hsiao, Pei Wen ; Yang, Ning Sun. / Immunogenicity of mammary tumor cells can be induced by shikonin via direct binding-interference with hnRNPA1. In: Oncotarget. 2016 ; Vol. 7, No. 28. pp. 43629-43653.
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