ArticlePLoS genetics2014
Scribble modulates the MAPK/Fra1 pathway to disrupt luminal and ductal integrity and suppress tumour formation in the mammary gland.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- FRA1 (Frontiers in cell and developmental biology · 2025Article
- Scribble Deficiency Promotes Pancreatic Ductal Adenocarcinoma Development and Metastasis.Cancer research · 2024Article
- Stearoylation cycle regulates the cell surface distribution of the PCP protein Vangl2.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cell polarity changes in cancer initiation and progression.The Journal of cell biology · 2024Review
- FRA-1 as a Regulator of EMT and Metastasis in Breast Cancer.International journal of molecular sciences · 2023Review
- RNA atlas and competing endogenous RNA regulation in tissue-derived exosomes from luminal B and triple-negative breast cancer patients.Frontiers in oncology · 2023Article
- Over-expression of miR-183-5p or miR-492 triggers invasion and proliferation and loss of polarity in non-neoplastic breast epithelium.Scientific reports · 2022Article
- Afadin couples RAS GTPases to the polarity rheostat Scribble.Nature communications · 2022Article
- Apical-basal polarity and the control of epithelial form and function.Nature reviews. Molecular cell biology · 2022Review
- A risk progression breast epithelial 3D culture model reveals Cx43/hsa_circ_0077755/miR-182 as a biomarker axis for heightened risk of breast cancer initiation.Scientific reports · 2021Article
- PtdIns(3,4,5)PProceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Scribble family in cancer: twentieth anniversary.Oncogene · 2020Review
- Scribble promotes alveologenesis in the pregnant mammary gland for milk production.Reproduction (Cambridge, England) · 2020Article
- Blockade of Adenosine A2b Receptor Reduces Tumor Growth and Migration in Renal Cell Carcinoma.Journal of Cancer · 2020Article
- Scribble, Erbin, and Lano redundantly regulate epithelial polarity and apical adhesion complex.The Journal of cell biology · 2019Article
- Connexin 43 maintains tissue polarity and regulates mitotic spindle orientation in the breast epithelium.Journal of cell science · 2019Article
- Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation.The Journal of cell biology · 2019Review
- Drosophila Models of Cell Polarity and Cell Competition in Tumourigenesis.Advances in experimental medicine and biology · 2019Review
- The SCRIB Paralog LANO/LRRC1 Regulates Breast Cancer Stem Cell Fate through WNT/β-Catenin Signaling.Stem cell reports · 2018Article
- High Expression of CD200 and CD200R1 Distinguishes Stem and Progenitor Cell Populations within Mammary Repopulating Units.Stem cell reports · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polarity coordinates cell movement, differentiation, proliferation and apoptosis to build and maintain complex epithelial tissues such as the mammary gland. Loss of polarity and the deregulation of these processes are critical events in malignant progression but precisely how and at which stage polarity loss impacts on mammary development and tumourigenesis is unclear. Scrib is a core polarity regulator and tumour suppressor gene however to date our understanding of Scrib function in the mammary gland has been limited to cell culture and transplantation studies of cell lines. Utilizing a conditional mouse model of Scrib loss we report for the first time that Scrib is essential for mammary duct morphogenesis, mammary progenitor cell fate and maintenance, and we demonstrate a critical and specific role for Scribble in the control of the early steps of breast cancer progression. In particular, Scrib-deficiency significantly induced Fra1 expression and basal progenitor clonogenicity, which resulted in fully penetrant ductal hyperplasia characterized by high cell turnover, MAPK hyperactivity, frank polarity loss with mixing of apical and basolateral membrane constituents and expansion of atypical luminal cells. We also show for the first time a role for Scribble in mammalian spindle orientation with the onset of mammary hyperplasia being associated with aberrant luminal cell spindle orientation and a failure to apoptose during the final stage of duct tubulogenesis. Restoring MAPK/Fra1 to baseline levels prevented Scrib-hyperplasia, whereas persistent Scrib deficiency induced alveolar hyperplasia and increased the incidence, onset and grade of mammary tumours. These findings, based on a definitive genetic mouse model provide fundamental insights into mammary duct maturation and homeostasis and reveal that Scrib loss activates a MAPK/Fra1 pathway that alters mammary progenitor activity to drive premalignancy and accelerate tumour progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.