Secreted HMGB1 from Wnt activated intestinal cells is required to maintain a crypt progenitor phenotype.

ABSTRACT:

Background and aims

Colorectal cancer (CRC) arises via multiple genetic changes. Mutation of the tumour suppressor gene APC, a key regulator of Wnt signalling, is recognised as a frequent early driving mutation in CRC. We have previously shown that conditional loss of Apc within the murine small intestine (Apcfloxmice) results in acute Wnt signalling activation, altered crypt-villus architecture and many hallmarks of neoplasia. Our transctipomic profiling (Affymetrix Microarrays) and proteomic profiling (iTRAQ-QSTAR) of Apc-deficient intestine inferred the involvement of High Mobility Group Box 1 (Hmgb1) in CRC pathogenesis. Here we assess the contribution of HMGB1 to the crypt progenitor phenotype seen following Apc loss.

Results

Elevated HMGB1 was confirmed in intestinal e

SUBMITTER: Reed KR 

PROVIDER: S-EPMC5239505 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature