Stimulatory role of nectin-4 and p95-ErbB2 in multilayered T47D cell proliferation.

Abstract

Multilayered proliferation in an adherent culture as well as proliferation in a suspension culture is a characteristic feature of cancer cells. We previously showed using T47D human mammary cancer cells that nectin-4, upregulated in many cancer cells, cis-interacts with ErbB2 and its trastuzumab-resistant splice variants, p95-ErbB2 and ErbB2ΔEx16, and enhances DNA synthesis mainly through the PI3K-AKT pathway in an adherent culture. We showed here that only the combination of nectin-4 and p95-ErbB2, but not that of nectin-4 and ErbB2 or that of nectin-4 and ErbB2ΔEx16, cooperatively enhanced multilayered T47D cell proliferation through the Hippo pathway-mediated SOX2 gene expression in an adherent culture. T47D cells expressed the components of the apical junctional complex (AJC) consisting of adherens junctions (AJs) and tight junctions and cell polarity molecules, but not the AJ component afadin. The AJC and apicobasal polarity were disorganized in T47D cells in a monolayer and T47D cells stably expressing both nectin-4 and p95-ErbB2 in multilayers. These results indicate that nectin-4 and p95-ErbB2 play a stimulatory role in multilayered proliferation in an adherent culture.

• Authors: Shin Kedashiro, Takeshi Kameyama, Kiyohito Mizutani, Yoshimi Takai
• Journal: Genes to cells : devoted to molecular & cellular mechanisms (Genes Cells) Vol. 27 Issue 6 Pg. 451-464 (Jun 2022) ISSN: 1365-2443 [Electronic] England
• PMID: 35430770 (Publication Type: Journal Article)
• Copyright: © 2022 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Chemical References

• Cadherins
• Cell Adhesion Molecules
• Nectins
• NECTIN4 protein, human
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adherens Junctions (drug effects)
• Breast Neoplasms (pathology)
• Cadherins (metabolism)
• Cell Adhesion (drug effects)
• Cell Adhesion Molecules (metabolism, pharmacology)
• Cell Proliferation (drug effects)
• Female
• Humans
• Nectins (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Receptor, ErbB-2 (metabolism)
• Tumor Cells, Cultured