Integrin a6 loss promotes colitis-associated colorectal cancer. Response to: "Integrin a6 variants and colorectal cancer" by Beaulieu JF

In a recently published letter,1 Dr Beaulieu questions our recent publication suggesting that α6 integrin acts as a tumour suppressor gene in colorectal cancer (CRC),2 given the apparent antagonistic role of α6A and α6B integrin isoforms in the intestine. We thank him for raising this important issue and welcome the opportunity of clarifying the topic. We showed that mice failing to express the α6 integrin (both α6A and α6B isoforms) specifically in intestinal epithelial cells (α6^IEC) spontaneously develop fully penetrant colitis and adenocarcinoma afterwards.2 These mice display epithelium detachment from the basement membrane, followed by oversecretion of interleukin (IL)-18 and IL-1β proinflammatory cytokines, infiltration of myeloid cells, and finally activation of the adaptive immunity, which mediates tumour progression. Thus, since α6^IEC mutant mice develop adenocarcinoma without any additional treatment, Itga6 behaves as a tumour suppressor gene (a gene that protects a cell from one step...

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