The basement membrane regulates the cellular localization and the cytoplasmic interactome of Yes-Associated Protein (YAP) in mammary epithelial cells.

Hippo YAP extracellular matrix mammary gland proteomics

Journal

Journal of cellular biochemistry
ISSN: 1097-4644
Titre abrégé: J Cell Biochem
Pays: United States
ID NLM: 8205768

Informations de publication

Date de publication:
23 May 2024
Historique:
revised: 16 04 2024
received: 23 10 2023
accepted: 08 05 2024
medline: 23 5 2024
pubmed: 23 5 2024
entrez: 23 5 2024
Statut: aheadofprint

Résumé

The Hippo pathway, a signaling cascade involved in the regulation of organ size and several other processes, acts as a conduit between extracellular matrix (ECM) cues and cellular responses. We asked whether the basement membrane (BM), a specialized ECM component known to induce quiescence and differentiation in mammary epithelial cells, would regulate the localization, activity, and interactome of YAP, a Hippo pathway effector. To address this question, we used a broad range of experimental approaches, including 2D and 3D cultures of both mouse and human mammary epithelial cells, as well as the developing mouse mammary gland. In contrast to malignant cells, nontumoral cells cultured with a reconstituted BM (rBM) displayed higher concentrations of YAP in the cytoplasm. Incidentally, when in the nucleus of rBM-treated cells, YAP resided preferentially at the nuclear periphery. In agreement with our cell culture experiments, YAP exhibited cytoplasmic predominance in ductal cells of developing mammary epithelia, where a denser BM is found. Conversely, terminal end bud (TEB) cells with a thinner BM displayed higher nucleus-to-cytoplasm ratios of YAP. Bioinformatic analysis revealed that genes regulated by YAP were overrepresented in the transcriptomes of microdissected TEBs. Consistently, mouse epithelial cells exposed to the rBM expressed lower levels of YAP-regulated genes, although the protein level of YAP and Hippo components were slightly altered by the treatment. Mass spectrometry analysis identified a differential set of proteins interacting with YAP in cytoplasmic fractions of mouse epithelial cells in the absence or presence of rBM. In untreated cells, YAP interactants were enriched in processes related to ubiquitin-mediated proteolysis, whereas in cells exposed to rBM YAP interactants were mainly key proteins related to amino acid, amino sugar, and carbohydrate metabolism. Collectively, we unraveled that the BM induces YAP translocation or retention in the cytoplasm of nontumoral epithelial cells and that in the cytoplasm YAP seems to undertake novel functions in metabolic pathways.

Identifiants

pubmed: 38779980
doi: 10.1002/jcb.30606
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Fundação de Amparo à Pesquisa do Estado de São Paulo

Informations de copyright

© 2024 Wiley Periodicals LLC.

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Auteurs

Antonio Carlos Manucci (AC)

Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.

Ana Paula Zen Petisco Fiore (APZP)

Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.

Giovani Luiz Genesi (GL)

Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.

Alexandre Bruni-Cardoso (A)

Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.

Classifications MeSH