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ERα/LKB1 complex upregulates E-cadherin expression and stimulates breast cancer growth and progression upon adiponectin exposure.
Naimo, Giuseppina Daniela; Forestiero, Martina; Paolì, Alessandro; Malivindi, Rocco; Gelsomino, Luca; Gyorffy, Balázs; Leonetti, Adele Elisabetta; Giordano, Francesca; Panza, Salvatore; Conforti, Francesca Luisa; Ruffo, Paola; Panno, Maria Luisa; Mauro, Loredana; Andò, Sebastiano.
Afiliación
  • Naimo GD; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  • Forestiero M; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  • Paolì A; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  • Malivindi R; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  • Gelsomino L; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  • Gyorffy B; Department of Bioinformatics, Semmelweis University, Budapest, Hungary.
  • Leonetti AE; Cancer Biomarker Research Group, Research Centre for Natural Sciences, Budapest, Hungary.
  • Giordano F; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  • Panza S; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  • Conforti FL; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  • Ruffo P; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  • Panno ML; Medical Genetics Laboratory, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  • Mauro L; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
  • Andò S; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
Int J Cancer ; 153(6): 1257-1272, 2023 09 15.
Article en En | MEDLINE | ID: mdl-37323038
Adiponectin is the major adipocytes-secreted protein involved in obesity-related breast cancer growth and progression. We proved that adiponectin promotes proliferation in ERα-positive breast cancer cells, through ERα transactivation and the recruitment of LKB1 as ERα-coactivator. Here, we showed that adiponectin-mediated ERα transactivation enhances E-cadherin expression. Thus, we investigated the molecular mechanism through which ERα/LKB1 complex may modulate the expression of E-cadherin, influencing tumor growth, progression and distant metastasis. We demonstrated that adiponectin increases E-cadherin expression in ERα-positive 2D and higher extent in 3D cultures. This occurs through a direct activation of E-cadherin gene promoter by ERα/LKB1-complex. The impact of E-cadherin on ERα-positive breast cancer cell proliferation comes from the evidence that in the presence of E-cadherin siRNA the proliferative effects of adiponectin is no longer noticeable. Since E-cadherin connects cell polarity and growth, we investigated if the adiponectin-enhanced E-cadherin expression could influence the localization of proteins cooperating in cell polarity, such as LKB1 and Cdc42. Surprisingly, immunofluorescence showed that, in adiponectin-treated MCF-7 cells, LKB1 and Cdc42 mostly colocalize in the nucleus, impairing their cytosolic cooperation in maintaining cell polarity. The orthotopic implantation of MCF-7 cells revealed an enhanced E-cadherin-mediated breast cancer growth induced by adiponectin. Moreover, tail vein injection of MCF-7 cells showed a higher metastatic burden in the lungs of mice receiving adiponectin-treated cells compared to control. From these findings it emerges that adiponectin treatment enhances E-cadherin expression, alters cell polarity and stimulates ERα-positive breast cancer cell growth in vitro and in vivo, sustaining higher distant metastatic burden.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adiponectina / Neoplasias Límite: Animals / Humans Idioma: En Revista: Int J Cancer Año: 2023 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adiponectina / Neoplasias Límite: Animals / Humans Idioma: En Revista: Int J Cancer Año: 2023 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos