Colorectal cancer (CRC) is one of the most frequent cancers and current treatments include surgery and chemotherapy, but recurrence occurs frequently (30-50% of the cases). The intestinal epithelium undergoes continuous renewal fueled by stem cells that are at the origin of CRC and account for therapeutic refractoriness, drug resistance and metastasis dissemination.

Several signalling pathways, including Wnt and Notch, regulate intestinal homeostasis and tumorigenesis. Our laboratory demonstrated the importance of the thyroid hormone signaling through its nuclear receptor TRα1 in intestinal homeostasis and tumor appearance, through its cross-talk with Wnt and Notch as well as other pathways. Specifically, our studies indicated that TRα1 perturbation deregulates these pathways and participates in tumor initiation and progression through an action on progenitors and on stem cells (SCs) (rev. in Sirakov et al, 2014, PMID: 24604390; Skah et al, 2017, PMID: 28069375; Frau et al, 2017, PMID: 28288904; Giolito et al 2022, PMID: 35947210). This action includes a direct effect on cancer SCs and their chemoresistant properties (Giolito et al, 2024, PMID: 38693105) as well as indirect effects through stromal cells (ongoing).

We are currently using complementary in vivo analyses in mouse models and ex vivo studies in organoid cultures to better define the mechanisms of TRα1-mediated impact on intestinal physiopathology.