title: Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b.
abstract: P85α, which acts as a tumour suppressor, is frequently found to be downregulated in various human cancers. However, the role of p85α in the tumour microenvironment is unknown. Here, we report that aberrantly low expression of p85α in breast cancer stroma is clinically relevant to breast cancer disease progression. Stromal fibroblasts can acquire the hallmarks of cancer-associated fibroblasts (CAFs) as a result of the loss of p85α expression. Paracrine Wnt10b from p85α-deficient fibroblasts can promote cancer progression via epithelial-to-mesenchymal transition (EMT) induced by the canonical Wnt pathway. Moreover, exosomes have a key role in paracrine Wnt10b transport from fibroblasts to breast cancer epithelial cells. Our results reveal that p85α expression in stromal fibroblasts haves a crucial role in regulating breast cancer tumourigenesis and progression by modifying stromal-epithelial crosstalk and remodelling the tumour microenvironment. Therefore, p85α can function as a tumour suppressor and represent a new candidate for diagnosis, prognosis and targeted therapy.
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Sino-France Laboratory for Drug Screening, Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D000072645:Cancer-Associated Fibroblasts / Q000201:enzymology* / Q000473:pathology; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D058543:Class Ia Phosphatidylinositol 3-Kinase; D018920:Coculture Techniques; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D019899:Paracrine Communication; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017154:Stromal Cells / Q000201:enzymology / Q000473:pathology; D059016:Tumor Microenvironment; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D058543:Class Ia Phosphatidylinositol 3-Kinase; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C491119:WNT10B protein, human; C588001:PIK3R1 protein, human