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The epithelial polarity axis controls the resting membrane potential and Cl- co-transport in breast glandular structures.
Urazaev, Albert K; Wang, Lei; Bai, Yunfeng; Adissu, Hibret A; Lelièvre, Sophie A.
Afiliação
  • Urazaev AK; Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
  • Wang L; School of Liberal Arts, Sciences and Education, Ivy Tech Community College, Lafayette, IN 47905, USA.
  • Bai Y; Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA.
  • Adissu HA; Department of Basic Medical Sciences, Purdue University, West Lafayette, IN 47907, USA.
  • Lelièvre SA; Purdue Institute for Cancer Research, West Lafayette, IN 47907, USA.
J Cell Sci ; 137(5)2024 03 01.
Article em En | MEDLINE | ID: mdl-37818620
ABSTRACT
The membrane potential (MP) controls cell homeostasis by directing molecule transport and gene expression. How the MP is set upon epithelial differentiation is unknown. Given that tissue architecture also controls homeostasis, we investigated the relationship between basoapical polarity and resting MP in three-dimensional culture of the HMT-3522 breast cancer progression. A microelectrode technique to measure MP and input resistance reveals that the MP is raised by gap junction intercellular communication (GJIC), which directs tight-junction mediated apical polarity, and is decreased by the Na+/K+/2Cl- (NKCC, encoded by SLC12A1 and SLC12A2) co-transporter, active in multicellular structures displaying basal polarity. In the tumor counterpart, the MP is reduced. Cancer cells display diminished GJIC and do not respond to furosemide, implying loss of NKCC activity. Induced differentiation of cancer cells into basally polarized multicellular structures restores widespread GJIC and NKCC responses, but these structures display the lowest MP. The absence of apical polarity, necessary for cancer onset, in the non-neoplastic epithelium is also associated with the lowest MP under active Cl- transport. We propose that the loss of apical polarity in the breast epithelium destabilizes cellular homeostasis in part by lowering the MP.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glândulas Mamárias Humanas Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glândulas Mamárias Humanas Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article