Wnt signaling encompasses β-catenin-dependent and -independent networks. How receptor context provides Wnt specificity in vivo to assimilate multiple concurrent Wnt inputs throughout development remains unclear. Here, we identified a refined expression pattern of Wnt/receptor combinations associated with the Wnt/β-catenin-independent pathway in mammary epithelial subpopulations. Moreover, we elucidated the function of the alternative Wnt receptor Ror2 in mammary development and provided evidence for coordination of this pathway with Wnt/β-catenin-dependent signaling in the mammary epithelium. Lentiviral short hairpin RNA (shRNA)-mediated depletion of Ror2 in vivo increased branching and altered the differentiation of the mammary epithelium. Microarray analyses identified distinct gene level alterations within the epithelial compartments in the absence of Ror2, with marked changes observed in genes associated with the actin cytoskeleton. Modeling of branching morphogenesis in vitro defined specific defects in cytoskeletal dynamics accompanied by Rho pathway alterations downstream of Ror2 loss. The current study presents a model of Wnt signaling coordination in vivo and assigns an important role for Ror2 in mammary development.
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http://dx.doi.org/10.1083/jcb.201408058 | DOI Listing |
Georgian Med News
October 2024
1Department of Obstetrics and Gynecology, National Hospital Organization Kyoto Medical Center, Kyoto city, Kyoto; 3Seeds Development and Research Platform Project, Japan Agency for Medical Research and Development (AMED), Chiyoda-ku, Tokyo; 4Kyoto University Graduate School of Medicine, Kyoto city, Kyoto, Japan.
Endosalpingiosis occurs in relatively young women. The incidence of endosalpingiosis exceeds that of other diseases affecting female tissues. As endosalpingiosis is a benign tumor, several women with endosalpingiosis are asymptomatic.
View Article and Find Full Text PDFBiochim Biophys Acta Rev Cancer
December 2024
Laboratory for Molecular Virology and Gene Therapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. Electronic address:
Aberrant gene expression due to dysfunction in proteins involved in transcriptional regulation is a hallmark of tumor development. Indeed, targeting transcriptional regulators represents an emerging approach in cancer therapeutics. Lens epithelium-derived growth factor (LEDGF/p75, PSIP1) is a co-transcriptional activator that tethers several proteins to the chromatin.
View Article and Find Full Text PDFJ Surg Oncol
December 2024
Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.
Background And Objectives: The tumor-associated stroma is an essential compartment in breast cancer, and collagen fiber organization in the stroma has been reported to be correlated with prognosis. In this study, we sought to evaluate collagen fiber characteristics in relation to pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients.
Methods: A total of 388 breast cancer patients receiving NAC were enrolled.
Breast Cancer Res
December 2024
Department of Pathology, University of California, San Francisco, San Francisco, CA, 94143, USA.
Background: Human mammary epithelial cell (HMEC) cultures encounter a stress-associated barrier termed stasis, during which most cells adopt a senescence-like phenotype. From these cultures, rare variants emerge from the basal epithelial population, re-initiating growth. Variants exhibit pre-malignant properties, including an aberrant epigenetic program that enables continued proliferation and acquisition of genetic changes.
View Article and Find Full Text PDFPathol Oncol Res
December 2024
Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary.
Invasive micropapillary carcinoma of the breast is characterized by clusters of cells presenting with inverted polarity. Although the apico-basal polarity is a fundamental property of the epithelium, the biological alterations leading to the inside-out pattern observed in invasive micropapillary carcinoma (IMPC) remain mostly unknown. The regulation of tight junctions in polarity formation and maintenance is acknowledged.
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