The SCRIB Paralog LANO/LRRC1 Regulates Breast Cancer Stem Cell Fate through WNT/beta-Catenin Signaling

Leonor Lopez Almeida (1) , Michael Sebbagh (1) , Francois Bertucci (1) , Pascal Finetti (1) , Julien Wicinski (1) , Sylvie Marchetto (1) , Remy Castellano (1) , Emmanuelle Josselin (1) , Emmanuelle Charafe-Jauffret (1) , Christophe Ginestier (1) , Jean-Paul Borg (1) , Marie-Josee Santoni (1)

1 CRCM - Centre de Recherche en Cancérologie de Marseille

Tumor initiation, progression, and therapeutic resistance have been proposed to originate from a subset of tumor cells, cancer stem cells (CSCs). However, the current understanding of the mechanisms involved in their self-renewal and tumor initiation capacity remains limited. Here, we report that expression of LANO/LRRC1, the vertebrate paralog of SCRIB tumor suppressor, is associated with a stem cell signature in normal and tumoral mammary epithelia. Through in vitro and in vivo experiments including a Lano/Lrrc1 knockout mouse model, we demonstrate its involvement in the regulation of breast CSC (bCSC) fate. Mechanistically, we demonstrate that Lano/LRRC1-depleted cells secrete increased levels of WNT ligands, which act in a paracrine manner to positively deregulate the WNT/beta-catenin pathway in bCSCs. In addition to describing the first function of LANO/LRRC1, our results suggest that its expression level could be used as a biomarker to stratify breast cancer patients who could benefit from WNT/beta-catenin signaling inhibitors.

Mots clés: breast cancer; stem cell; LANO/LRRC1; SCRIB; Wnt/β-catenin; tumor suppressor

Domaines: Sciences du Vivant [q-bio]

Leonor Lopez Almeida, Michael Sebbagh, Francois Bertucci, Pascal Finetti, Julien Wicinski, et al.. The SCRIB Paralog LANO/LRRC1 Regulates Breast Cancer Stem Cell Fate through WNT/beta-Catenin Signaling. Stem Cell Reports, 2018, 11 (5), pp.1040-1050. ⟨10.1016/j.stemcr.2018.09.008⟩. ⟨hal-02143631⟩