FAT1: A potential target for monoclonal antibody therapy in colon cancer

Piero Pileri, Susanna Campagnoli, Alberto Grandi, Matteo Parri, Elisa De Camilli, Chaojun Song, Luisa Ganfini, Aurelien Lacombe, Ilaria Naldi, Paolo Sarmientos, Caterina Cinti, Boquan Jin, Guido Grandi, Giuseppe Viale, Luigi Terracciano, Renata Grifantini

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Colorectal cancer (CRC) is one of the major causes of cancer-associated mortality worldwide. The currently approved therapeutic agents have limited efficacy. Methods: The atypical cadherin FAT1 was discovered as a novel CRC-associated protein by using a monoclonal antibody (mAb198.3). FAT1 expression was assessed in CRC cells by immunohistochemistry (IHC), immunoblots, flow cytometry and confocal microscopy. In addition, in vitro and in vivo tumour models were done to assess FAT1 potential value for therapeutic applications. Results: The study shows that FAT1 is broadly expressed in primary and metastatic CRC stages and detected by mAb198.3, regardless of KRAS and BRAF mutations. FAT1 mainly accumulates at the plasma membrane of cancer cells, whereas it is only marginally detected in normal human samples. Moreover, the study shows that FAT1 has an important role in cell invasiveness while it does not significantly influence apoptosis. mAb198.3 specifically recognises FAT1 on the surface of colon cancer cells and is efficiently internalised. Furthermore, it reduces cancer growth in a colon cancer xenograft model. Conclusions: This study provides evidence that FAT1 and mAb198.3 may offer new therapeutic opportunities for CRC including the tumours resistant to current EGFR-targeted therapies.

Original languageEnglish
Pages (from-to)40-51
Number of pages12
JournalBritish Journal of Cancer
Volume115
Issue number1
DOIs
Publication statusPublished - Jun 28 2016

Keywords

  • BRAF
  • colorectal cancer
  • FAT1
  • immunohistochemistry
  • KRAS
  • monoclonal antibody

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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