TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype.

ABSTRACT: The heterogeneous nature of colorectal cancer (CRC) complicates prognosis and is suggested to be a determining factor in the efficacy of adjuvant therapy for individual patients. Based on gene expression profiling, CRC is currently classified into four consensus molecular subtypes (CMSs), characterized by specific biological programs, thus suggesting the existence of unifying developmental drivers for each CMS Using human organoid cultures, we investigated the role of such developmental drivers at the premalignant stage of distinct CRC subtypes and found that TGFβ plays an important role in the development of the mesenchymal CMS4, which is of special interest due to its association with dismal prognosis. We show that in tubular adenomas (TAs), which progress to classical CRCs, the dominati

SUBMITTER: Fessler E 

PROVIDER: S-EPMC4931289 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature