A complex of α6 integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6

Serena Marchiò, Marco Soster, Sabrina Cardaci, Andrea Muratore, Alice Bartolini, Vanessa Barone, Dario Ribero, Maria Monti, Paola Bovino, Jessica Sun, Raffaella Giavazzi, Sofia Asioli, Paola Cassoni, Lorenzo Capussotti, Piero Pucci, Antonella Bugatti, Marco Rusnati, Renata Pasqualini, Wadih Arap, Federico Bussolino

Research output: Contribution to journalArticle

Abstract

Homing of colorectal cancer (CRC) cells to the liver is a non-random process driven by a crosstalk between tumour cells and components of the host tissue. Here we report the isolation of a liver metastasis-specific peptide ligand (CGIYRLRSC) that binds a complex of E-cadherin and α6 integrin on the surface of CRC cells. We identify angiopoietin-like 6 protein as a peptide-mimicked natural ligand enriched in hepatic blood vessels of CRC patients. We demonstrate that an interaction between hepatic angiopoietin-like 6 and tumoural α6 integrin/E-cadherin drives liver homing and colonization by CRC cells, and that CGIYRLRSC inhibits liver metastasis through interference with this ligand/receptor system. Our results indicate a mechanism for metastasis whereby a soluble factor accumulated in normal vessels functions as a specific ligand for circulating cancer cells. Consistently, we show that high amounts of coexpressed α6 integrin and E-cadherin in primary tumours represent a poor prognostic factor for patients with advanced CRC.

Original languageEnglish
Pages (from-to)1156-1175
Number of pages20
JournalEMBO Molecular Medicine
Volume4
Issue number11
DOIs
Publication statusPublished - Nov 2012

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Keywords

  • α integrin
  • Angiopoietin-like 6
  • E-cadherin
  • Metastatic colorectal cancer
  • Microenvironment

ASJC Scopus subject areas

  • Molecular Medicine

Cite this

Marchiò, S., Soster, M., Cardaci, S., Muratore, A., Bartolini, A., Barone, V., Ribero, D., Monti, M., Bovino, P., Sun, J., Giavazzi, R., Asioli, S., Cassoni, P., Capussotti, L., Pucci, P., Bugatti, A., Rusnati, M., Pasqualini, R., Arap, W., & Bussolino, F. (2012). A complex of α6 integrin and E-cadherin drives liver metastasis of colorectal cancer cells through hepatic angiopoietin-like 6. EMBO Molecular Medicine, 4(11), 1156-1175. https://doi.org/10.1002/emmm.201101164