The water channels Aquaporin-1 and Aquaporin-3 interact with and affect the cell polarity protein Scribble in 3D in vitro models of breast cancer

TY - JOUR

T1 - The water channels Aquaporin-1 and Aquaporin-3 interact with and affect the cell polarity protein Scribble in 3D in vitro models of breast cancer

AU - E, Sarannya

AU - Login, Frédéric H.

AU - Riishede, Andreas

AU - Dam, Vibeke Secher

AU - Jensen, Teresa Kirkegaard

AU - Nejsum, Lene Niemann

PY - 2024/11/1

Y1 - 2024/11/1

N2 - Cellular changes in carcinomas include alterations in cell proliferation, cell migration, cell-cell adhesion, and cellular polarity. In vitro studies have revealed that the water channels, aquaporin-1 (AQP1) and AQP3, can influence cell migration and cellcell adhesion. Of note, we previously showed that AQP1 overexpression reduced levels of cell-cell adhesion proteins, whereas AQP3 increased levels when overexpressed in normal epithelial cells. Expression of AQP1 and AQP3 in breast carcinoma is associated with lymph node metastasis, recurrence, and poor survival of patients with breast cancer. In this study, we investigated if AQP1 and AQP3 affected cell polarity in breast cancer by studying the relationship between the major polarity protein Scribble and AQP1 and AQP3. In breast cancer tissue samples, the protein expression of AQP1, AQP3, and Scribble did not show an obvious correlation. However, in a GST pull-down assay, AQP1 and AQP3 interacted with Scribble. AQP1 overexpression reduced the size of 3D spheroids as well as reduced Scribble levels at cell-cell contacts, whereas AQP3 overexpression showed no significant change in spheroid size compared with control, AQP3 overexpression also reduced Scribble levels at cell-cell contacts. Of note, AQP1 overexpression increased cell migration and induced cell detachment and dissemination from migrating breast cancer cell sheets, whereas AQP3 overexpression did not. Thus, AQP1 and AQP3 differentially affect 3D-grown breast cancer spheroids, and especially AQP1 may contribute to cancer development and spread via negatively affecting cellular junctions and cell polarity proteins as well as increasing cell migration and cell detachment.

AB - Cellular changes in carcinomas include alterations in cell proliferation, cell migration, cell-cell adhesion, and cellular polarity. In vitro studies have revealed that the water channels, aquaporin-1 (AQP1) and AQP3, can influence cell migration and cellcell adhesion. Of note, we previously showed that AQP1 overexpression reduced levels of cell-cell adhesion proteins, whereas AQP3 increased levels when overexpressed in normal epithelial cells. Expression of AQP1 and AQP3 in breast carcinoma is associated with lymph node metastasis, recurrence, and poor survival of patients with breast cancer. In this study, we investigated if AQP1 and AQP3 affected cell polarity in breast cancer by studying the relationship between the major polarity protein Scribble and AQP1 and AQP3. In breast cancer tissue samples, the protein expression of AQP1, AQP3, and Scribble did not show an obvious correlation. However, in a GST pull-down assay, AQP1 and AQP3 interacted with Scribble. AQP1 overexpression reduced the size of 3D spheroids as well as reduced Scribble levels at cell-cell contacts, whereas AQP3 overexpression showed no significant change in spheroid size compared with control, AQP3 overexpression also reduced Scribble levels at cell-cell contacts. Of note, AQP1 overexpression increased cell migration and induced cell detachment and dissemination from migrating breast cancer cell sheets, whereas AQP3 overexpression did not. Thus, AQP1 and AQP3 differentially affect 3D-grown breast cancer spheroids, and especially AQP1 may contribute to cancer development and spread via negatively affecting cellular junctions and cell polarity proteins as well as increasing cell migration and cell detachment.

KW - Aquaporin 1/metabolism

KW - Aquaporin 3/metabolism

KW - Breast Neoplasms/pathology

KW - Cell Adhesion

KW - Cell Line, Tumor

KW - Cell Movement

KW - Cell Polarity

KW - Female

KW - Humans

KW - MCF-7 Cells

KW - Membrane Proteins/metabolism

KW - Spheroids, Cellular/metabolism

KW - Tumor Suppressor Proteins/metabolism

KW - AQP

KW - Scribble

KW - breast cancer

KW - aquaporin

KW - polarity

UR - http://www.scopus.com/inward/record.url?scp=85208204167&partnerID=8YFLogxK

U2 - 10.1152/ajpcell.00094.2024

DO - 10.1152/ajpcell.00094.2024

M3 - Journal article

C2 - 39279492

SN - 0363-6143

VL - 327

SP - C1323-C1334

JO - American Journal of Physiology: Cell Physiology

JF - American Journal of Physiology: Cell Physiology

IS - 5

ER -