PIAS1 is not suitable as a urothelial carcinoma biomarker protein and pharmacological target

PLoS One. 2019 Oct 22;14(10):e0224085. doi: 10.1371/journal.pone.0224085. eCollection 2019.

Abstract

Urothelial cancer (UC) is one of the most common cancers in Europe and is also one of the costliest to treat. When first line therapies show initial success, around 50% of cancers relapse and proceed to metastasis. In this study we assessed the Protein inhibitor of activated signal transducers and activators of transcription (PIAS)1 as a potential therapeutic target in urothelial cancer. PIAS1 is a key regulator of STAT1 signalling and may be implicated in carcinogenesis. In contrast to other cancer types PIAS1 protein expression is not significantly different in malignant areas of UC specimens compared to non-malignant tissue. In addition, we found that down-regulation and overexpression of PIAS1 had no effect on the viability or colony forming ability of tested cell lines. Whilst other studies of PIAS1 suggest an important biological role in cancer, this study shows that PIAS1 has no influence on reducing the cytotoxic effects of Cisplatin or cell recovery after DNA damage induced by irradiation. Taken together, these in vitro data demonstrate that PIAS1 is not a promising therapeutic target in UC cancer as previously shown in different entities such as prostate cancer (PCa).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Proliferation / drug effects*
  • Cisplatin / pharmacology*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology*
  • Prognosis
  • Protein Inhibitors of Activated STAT / genetics*
  • Protein Inhibitors of Activated STAT / metabolism
  • Small Ubiquitin-Related Modifier Proteins / genetics*
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Survival Rate
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay
  • Urologic Neoplasms / drug therapy
  • Urologic Neoplasms / genetics
  • Urologic Neoplasms / pathology*

Substances

  • Antineoplastic Agents
  • PIAS1 protein, human
  • Protein Inhibitors of Activated STAT
  • Small Ubiquitin-Related Modifier Proteins
  • Cisplatin

Grant support

This work was supported by the intramural research grant of the Medical University Mainz/Germany given to HE.