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 journalArticlepeer-review

16 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

Keywords

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

ASJC Scopus subject areas

  • Oncology

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