Dataset Information

PI3K-AKT pathway and cell-cell contact regulates maspin nuclear localization

ABSTRACT: Background: Maspin (SERPINB5) is a potential tumor suppressor gene with pleiotropic biological activities, including regulation of cell proliferation, death, adhesion, migration and gene expression. Several studies indicate that nuclear localization is essential for maspin tumor suppression activity. We have previously shown that the EGFR activation leads to maspin nuclear localization in MCF-10A cells. The present study investigated which EGFR downstream signaling molecules are involved in maspin nuclear localization and explored a possible role of cell-cell contact in this process. Methods: MCF-10A cells were treated with pharmacological inhibitors against EGFR downstream pathways followed by EGF treatment. Maspin subcellular localization was determined by immunofluorescence. To investigate the role of cell-cell contact these cells were either treated with chelating agents or plated on different cell densities. Maspin and E-cadherin subcellular localization was determined by immunofluorescence. In addition, proteomic and interactome analyses were conducted in order to identify molecular partners which interact with maspin in EGF-treated cells only. Results: EGFR activation regulates cell behavior via de extracellular signal–related kinase (ERK)/MAP kinase, phosphatidyl-inositol-3 (PI 3) kinase- AKT and Jak-STAT pathways. Using pharmacological inhibitors against key components of these signaling pathways we found that PI3K-AKT and Jak-STAT, but not MAP kinase pathway, regulate EGF-induced maspin nuclear accumulation in MCF-10A cells. Interestingly, we observed that maspin is predominantly nuclear in sparse cell culture, but it is redistributed to the cytoplasm in confluent cells even in the presence of EGF. Proteomic and interactome results suggest a role of maspin on post-transcriptional and translation regulation, protein folding and cell-cell adhesion.Conclusions: Maspin nuclear accumulation is determined by an interplay between EGFR (via PI3K-AKT and Jak-STAT pathways) and cell-to-cell contact.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Disease Free

SUBMITTER: Julia Cunha

LAB HEAD: Nathalie Cella

PROVIDER: PXD023224 | Pride | 2021-09-09

REPOSITORIES: Pride

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			Action	DRS
	OB_JC_NATHALIE_15__MASP_IP1_04.raw	Raw
	OB_JC_NATHALIE_15__MASP_IP2_05.raw	Raw
	OB_JC_NATHALIE_15__MASP_IP3_06.raw	Raw
	OB_JC_NATHALIE_5__IP1_01.raw	Raw
	OB_JC_NATHALIE_5__IP2_02.raw	Raw

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Publications

PI3K-AKT, JAK2-STAT3 pathways and cell-cell contact regulate maspin subcellular localization.

Longhi M T MT Silva L E LE Pereira M M Magalhães M M Reina J J Vitorino F N L FNL Gumbiner B M BM da Cunha J P C JPC Cella N N

Cell communication and signaling : CCS 20210814 1

<h4>Background</h4>Maspin (SERPINB5) is a potential tumor suppressor gene with pleiotropic biological activities, including regulation of cell proliferation, death, adhesion, migration and gene expression. Several studies indicate that nuclear localization is essential for maspin tumor suppression activity. We have previously shown that the EGFR activation leads to maspin nuclear localization in MCF-10A cells. The present study investigated which EGFR downstream signaling molecules are involved ...[more]

PMID: 34391444

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