CD151 regulates expression of FGFR2 in breast cancer cells via PKC-dependent pathways

Research output: Contribution to journalArticle

Authors

  • Rafal Sadej
  • Lukasz Torczyk
  • Andrea Lopez-Clavijo
  • Radzisław Kordek
  • Piotr Potemski
  • Michael Wakelam
  • Hanna Romanska

External organisations

  • Department of Molecular Enzymology, Medical University of Gdańsk
  • Department of Pathology and Chemotherapy, Medical University of Łόdź
  • The Babraham Institute; Babraham Research Campus; UK
  • Babraham Institute; Babraham Research Campus; Cambridge United Kingdom

Abstract

Expression of the tetraspanin CD151 is frequently upregulated in epithelial malignancies and correlates with poor prognosis. Here we report that CD151 is involved in regulation of the expression of fibroblast growth factor receptor 2 (FGFR2). Depletion of CD151 in breast cancer cells resulted in an increased level of FGFR2. Accordingly, an inverse correlation between CD151 and FGFR2 was observed in breast cancer tissues. CD151-dependent regulation of the FGFR2 expression relies on post-transcriptional mechanisms involving HuR/ELAVL1, a multifunctional RNA binding protein, and the assembly of processing bodies (P-bodies). Depletion of CD151 correlated with inhibition of PKC, a well-established downstream target of CD151. Accordingly, the levels of dialcylglycerol species were decreased in CD151-negative cells, and inhibition of PKC resulted in the increased expression of FGFR2. Whilst expression of FGFR2 itself did not correlate with any of the clinicopathological data, the FGFR2-/CD151+ patients are more likely to develop lymph node metastasis. Conversely, FGFR2-/CD151- patients demonstrated better overall survival. These results illustrate functional interdependency between CD151 complexes and FGFR2 and suggest a previously unsuspected role of CD151 in breast tumourigenesis.

Details

Original languageEnglish
Article numberjcs220640
JournalJournal of Cell Science
Volume131
Publication statusPublished - 29 Oct 2018

Keywords

  • CD151, FGFR2, breast cancer, tetraspanin, PKC