Star-PAP, a poly(A) polymerase, functions as a tumor suppressor in an orthotopic human breast cancer model

Cell Death Dis. 2017 Feb 2;8(2):e2582. doi: 10.1038/cddis.2016.199.

Abstract

Star-PAP is a noncanonical poly(A) polymerase and required for the expression of a select set of mRNAs. However, the pathological role of Star-PAP in cancer largely remains unknown. In this study, we observed decreased expression of Star-PAP in breast cancer cell lines and tissues. Ectopic Star-PAP expression inhibited proliferation as well as colony-forming ability of breast cancer cells. In breast cancer patients, high levels of Star-PAP correlated with an improved prognosis. Moreover, by regulating the expression of BIK (BCL2-interacting killer), Star-PAP induced apoptosis of breast cancer cells through the mitochondrial pathway. The growth of breast cancer xenografts in NOD/SCID mice was also inhibited by the doxycycline-induced Star-PAP overexpression. Furthermore, Star-PAP sensitized breast cancer cells to chemotherapy drugs both in vitro and in vivo. In mammary epithelial cells, Star-PAP knockdown partially transformed these cells and induced them to undergo epithelial-mesenchymal transition (EMT). These findings suggested that Star-PAP possesses tumor-suppressing activity and can be a valuable target for developing new cancer therapeutic strategies.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins / metabolism
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Doxycycline / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Nucleotidyltransferases
  • Polynucleotide Adenylyltransferase / metabolism*
  • RNA, Messenger / metabolism
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • Nucleotidyltransferases
  • TUT1 protein, human
  • Polynucleotide Adenylyltransferase
  • Doxycycline