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/β-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/β-catenin signaling inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234904 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2018.09.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CDKN3 as a key regulator of G2M phase in triple-negative breast cancer: Insights from multi-transcriptomic analysis.
IUBMB Life
January 2025
Precision Medicine Laboratory, School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China.
Triple-negative breast cancer (TNBC) remains a significant global health challenge, emphasizing the need for precise identification of patients with specific therapeutic targets and those at high risk of metastasis. This study aimed to identify novel therapeutic targets for personalized treatment of TNBC patients by elucidating their roles in cell cycle regulation. Using weighted gene co-expression network analysis (WGCNA), we identified 83 hub genes by integrating gene expression profiles with clinical pathological grades.
View Article and Find Full Text PDFAn analysis of multilevel factor contributions to breast cancer screening inequities in an academic health system.
Cancer
February 2025
General Medicine Service, VA Puget Sound Health Care System, Seattle, Washington, USA.
Background: Breast cancer screening (BCS) inequities are evident at national and local levels, and many health systems want to address these inequities, but may lack data about contributing factors. The objective of this study was to inform health system interventions through an exploratory analysis of potential multilevel contributors to BCS inequities using health system data.
Methods: The authors conducted a cross-sectional analysis within a large academic health system including 19,774 individuals who identified as Black (n = 1445) or White (n = 18,329) race and were eligible for BCS.
POLE mutations in endometrial carcinoma: Clinical and genomic landscape from a large prospective single-center cohort.
Cancer
February 2025
Departmental Unit of Molecular and Genomic Diagnostics, Genomics Core Facility, G-STeP, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Background: To date, 11 DNA polymerase epsilon (POLE) pathogenic variants have been declared "hotspot" mutations. Patients with endometrial cancer (EC) characterized by POLE hotspot mutations (POLEmut) have exceptional survival outcomes. Whereas international guidelines encourage deescalation of adjuvant treatment in early-stage POLEmut EC, data regarding safety in POLEmut patients with unfavorable characteristics are still under investigation.
View Article and Find Full Text PDFAdjusting for Ascertainment Bias in Meta-Analysis of Penetrance for Cancer Risk.
Stat Med
February 2025
Department of Mathematical Sciences, University of Texas at Dallas, Richardson, Texas, USA.
Multi-gene panel testing allows efficient detection of pathogenic variants in cancer susceptibility genes including moderate-risk genes such as ATM and PALB2. A growing number of studies examine the risk of breast cancer (BC) conferred by pathogenic variants of these genes. A meta-analysis combining the reported risk estimates can provide an overall estimate of age-specific risk of developing BC, that is, penetrance for a gene.
View Article and Find Full Text PDFA rare intersection: squamous cell carcinoma of the tonsil and the anti-TIF1 syndrome masquerade.
BMC Rheumatol
January 2025
Department of Rheumatology, Overton Brooks VA Medical Center, Shreveport, LA, USA.
Background: Dermatomyositis is a chronic inflammatory condition affecting muscles and skin, often associated with an increased risk of cancer. Specific autoantibodies, including anti-TIF1 (Transcription Intermediary Factor 1), have been linked to this risk. We present a case of dermatomyositis in a male patient positive for anti-TIF1 antibodies, subsequently diagnosed with squamous cell carcinoma of the tonsil, a novel association not previously documented.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!