Aquaporin-3 controls breast cancer cell migration by regulating hydrogen peroxide transport and its downstream cell signaling

Hiroki Satooka, Mariko Chikuma

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Most breast cancer mortality is due to clinical relapse associated with metastasis. CXCL12/CXCR4-dependent cell migration is a critical process in breast cancer progression; however, its underlying mechanism remains to be elucidated. Here, we show that the water/glycerol channel protein aquaporin-3 (AQP3) is required for CXCL12/CXCR4-dependent breast cancer cell migration through a mechanism involving its hydrogen peroxide (H2O2) transport function. Extracellular H2O2, produced by CXCL12- activated membrane NADPH oxidase 2 (Nox2), was transported into breast cancer cells via AQP3. Transient H2O2 accumulation was observed around the membrane during CXCL12-induced migration, which may be facilitated by the association of AQP3 with Nox2. Intracellular H2O2 then oxidized PTEN and protein tyrosine phosphatase 1B (PTP1B) followed by activation of the Akt pathway. This contributed to directional cell migration. The expression level of AQP3 in breast cancer cells was related to their migration ability both in vitro and in vivo through CXCL12/CXCR4- or H2O2-dependent pathways. Coincidentally, spontaneous metastasis of orthotopic xenografts to the lung was reduced upon AQP3 knockdown. These findings underscore the importance of AQP3-transported H2O2 in CXCL12/CXCR4-dependent signaling and migration in breast cancer cells and suggest that AQP3 has potential as a therapeutic target for breast cancer.

Original languageEnglish
Pages (from-to)1206-1218
Number of pages13
JournalMolecular and Cellular Biology
Volume36
Issue number7
DOIs
Publication statusPublished - 2016 Apr 1
Externally publishedYes

Fingerprint

Aquaporin 3
Hydrogen Peroxide
Cell Movement
Breast Neoplasms
NADPH Oxidase
Non-Receptor Type 1 Protein Tyrosine Phosphatase
PTEN Phosphohydrolase
Neoplasm Metastasis
Aquaporins
Membranes
Heterografts
Glycerol
Recurrence
Lung
Mortality

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Aquaporin-3 controls breast cancer cell migration by regulating hydrogen peroxide transport and its downstream cell signaling. / Satooka, Hiroki; Chikuma, Mariko.

In: Molecular and Cellular Biology, Vol. 36, No. 7, 01.04.2016, p. 1206-1218.

Research output: Contribution to journalArticle

@article{514de762d8364c9b876032cbb6e476c6,
title = "Aquaporin-3 controls breast cancer cell migration by regulating hydrogen peroxide transport and its downstream cell signaling",
abstract = "Most breast cancer mortality is due to clinical relapse associated with metastasis. CXCL12/CXCR4-dependent cell migration is a critical process in breast cancer progression; however, its underlying mechanism remains to be elucidated. Here, we show that the water/glycerol channel protein aquaporin-3 (AQP3) is required for CXCL12/CXCR4-dependent breast cancer cell migration through a mechanism involving its hydrogen peroxide (H2O2) transport function. Extracellular H2O2, produced by CXCL12- activated membrane NADPH oxidase 2 (Nox2), was transported into breast cancer cells via AQP3. Transient H2O2 accumulation was observed around the membrane during CXCL12-induced migration, which may be facilitated by the association of AQP3 with Nox2. Intracellular H2O2 then oxidized PTEN and protein tyrosine phosphatase 1B (PTP1B) followed by activation of the Akt pathway. This contributed to directional cell migration. The expression level of AQP3 in breast cancer cells was related to their migration ability both in vitro and in vivo through CXCL12/CXCR4- or H2O2-dependent pathways. Coincidentally, spontaneous metastasis of orthotopic xenografts to the lung was reduced upon AQP3 knockdown. These findings underscore the importance of AQP3-transported H2O2 in CXCL12/CXCR4-dependent signaling and migration in breast cancer cells and suggest that AQP3 has potential as a therapeutic target for breast cancer.",
author = "Hiroki Satooka and Mariko Chikuma",
year = "2016",
month = "4",
day = "1",
doi = "10.1128/MCB.00971-15",
language = "English",
volume = "36",
pages = "1206--1218",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Aquaporin-3 controls breast cancer cell migration by regulating hydrogen peroxide transport and its downstream cell signaling

AU - Satooka, Hiroki

AU - Chikuma, Mariko

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Most breast cancer mortality is due to clinical relapse associated with metastasis. CXCL12/CXCR4-dependent cell migration is a critical process in breast cancer progression; however, its underlying mechanism remains to be elucidated. Here, we show that the water/glycerol channel protein aquaporin-3 (AQP3) is required for CXCL12/CXCR4-dependent breast cancer cell migration through a mechanism involving its hydrogen peroxide (H2O2) transport function. Extracellular H2O2, produced by CXCL12- activated membrane NADPH oxidase 2 (Nox2), was transported into breast cancer cells via AQP3. Transient H2O2 accumulation was observed around the membrane during CXCL12-induced migration, which may be facilitated by the association of AQP3 with Nox2. Intracellular H2O2 then oxidized PTEN and protein tyrosine phosphatase 1B (PTP1B) followed by activation of the Akt pathway. This contributed to directional cell migration. The expression level of AQP3 in breast cancer cells was related to their migration ability both in vitro and in vivo through CXCL12/CXCR4- or H2O2-dependent pathways. Coincidentally, spontaneous metastasis of orthotopic xenografts to the lung was reduced upon AQP3 knockdown. These findings underscore the importance of AQP3-transported H2O2 in CXCL12/CXCR4-dependent signaling and migration in breast cancer cells and suggest that AQP3 has potential as a therapeutic target for breast cancer.

AB - Most breast cancer mortality is due to clinical relapse associated with metastasis. CXCL12/CXCR4-dependent cell migration is a critical process in breast cancer progression; however, its underlying mechanism remains to be elucidated. Here, we show that the water/glycerol channel protein aquaporin-3 (AQP3) is required for CXCL12/CXCR4-dependent breast cancer cell migration through a mechanism involving its hydrogen peroxide (H2O2) transport function. Extracellular H2O2, produced by CXCL12- activated membrane NADPH oxidase 2 (Nox2), was transported into breast cancer cells via AQP3. Transient H2O2 accumulation was observed around the membrane during CXCL12-induced migration, which may be facilitated by the association of AQP3 with Nox2. Intracellular H2O2 then oxidized PTEN and protein tyrosine phosphatase 1B (PTP1B) followed by activation of the Akt pathway. This contributed to directional cell migration. The expression level of AQP3 in breast cancer cells was related to their migration ability both in vitro and in vivo through CXCL12/CXCR4- or H2O2-dependent pathways. Coincidentally, spontaneous metastasis of orthotopic xenografts to the lung was reduced upon AQP3 knockdown. These findings underscore the importance of AQP3-transported H2O2 in CXCL12/CXCR4-dependent signaling and migration in breast cancer cells and suggest that AQP3 has potential as a therapeutic target for breast cancer.

UR - http://www.scopus.com/inward/record.url?scp=84962148498&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962148498&partnerID=8YFLogxK

U2 - 10.1128/MCB.00971-15

DO - 10.1128/MCB.00971-15

M3 - Article

C2 - 26830227

AN - SCOPUS:84962148498

VL - 36

SP - 1206

EP - 1218

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 7

ER -