TRPM7 is required for breast tumor cell metastasis

Jeroen Middelbeek; Arthur J Kuipers; Linda Henneman; Daan Visser; Ilse Eidhof; Remco van Horssen; Bé Wieringa; Sander V Canisius; Wilbert Zwart; Lodewyk F Wessels; Fred C G J Sweep; Peter Bult; Paul N Span; Frank N van Leeuwen; Kees Jalink

doi:10.1158/0008-5472.CAN-11-3863

TRPM7 is required for breast tumor cell metastasis

Jeroen Middelbeek, Arthur J Kuipers, Linda Henneman, Daan Visser, Ilse Eidhof, Remco van Horssen, Bé Wieringa, Sander V Canisius, Wilbert Zwart, Lodewyk F Wessels, Fred C G J Sweep, Peter Bult, Paul N Span, Frank N van Leeuwen, Kees Jalink

Research output: Contribution to journal › Article › peer-review

192 Citations (Scopus)

Abstract

TRPM7 encodes a Ca2+-permeable nonselective cation channel with kinase activity. TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been established. Here we report that high levels of TRPM7 expression independently predict poor outcome in breast cancer patients and that it is functionally required for metastasis formation in a mouse xenograft model of human breast cancer. Mechanistic investigation revealed that TRPM7 regulated myosin II-based cellular tension, thereby modifying focal adhesion number, cell-cell adhesion and polarized cell movement. Our findings therefore suggest that TRPM7 is part of a mechanosensory complex adopted by cancer cells to drive metastasis formation.

Original language	English
Pages (from-to)	4250-61
Number of pages	12
Journal	Cancer research
Volume	72
Issue number	16
DOIs	https://doi.org/10.1158/0008-5472.CAN-11-3863
Publication status	Published - 15 Aug 2012
Externally published	Yes

Keywords

Animals
Breast Neoplasms/genetics
Cell Adhesion/physiology
Cell Line, Tumor
Cell Movement/physiology
Cytoskeleton/drug effects
Disease Progression
Female
Gene Knockdown Techniques
Humans
Mice
Mice, Transgenic
Neoplasm Metastasis
Neoplasm Staging
Protein Serine-Threonine Kinases
RNA, Messenger/biosynthesis
Receptors, Estrogen/biosynthesis
TRPM Cation Channels/biosynthesis

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10.1158/0008-5472.CAN-11-3863

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title = "TRPM7 is required for breast tumor cell metastasis",

abstract = "TRPM7 encodes a Ca2+-permeable nonselective cation channel with kinase activity. TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been established. Here we report that high levels of TRPM7 expression independently predict poor outcome in breast cancer patients and that it is functionally required for metastasis formation in a mouse xenograft model of human breast cancer. Mechanistic investigation revealed that TRPM7 regulated myosin II-based cellular tension, thereby modifying focal adhesion number, cell-cell adhesion and polarized cell movement. Our findings therefore suggest that TRPM7 is part of a mechanosensory complex adopted by cancer cells to drive metastasis formation.",

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author = "Jeroen Middelbeek and Kuipers, {Arthur J} and Linda Henneman and Daan Visser and Ilse Eidhof and {van Horssen}, Remco and B{\'e} Wieringa and Canisius, {Sander V} and Wilbert Zwart and Wessels, {Lodewyk F} and Sweep, {Fred C G J} and Peter Bult and Span, {Paul N} and {van Leeuwen}, {Frank N} and Kees Jalink",

note = "{\textcopyright}2012 AACR.",

year = "2012",

month = aug,

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doi = "10.1158/0008-5472.CAN-11-3863",

language = "English",

volume = "72",

pages = "4250--61",

journal = "Cancer research",

issn = "0008-5472",

publisher = "American Association for Cancer Research Inc.",

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AU - Middelbeek, Jeroen

AU - Kuipers, Arthur J

AU - Henneman, Linda

AU - Visser, Daan

AU - Eidhof, Ilse

AU - van Horssen, Remco

AU - Wieringa, Bé

AU - Canisius, Sander V

AU - Zwart, Wilbert

AU - Wessels, Lodewyk F

AU - Sweep, Fred C G J

AU - Bult, Peter

AU - Span, Paul N

AU - van Leeuwen, Frank N

AU - Jalink, Kees

PY - 2012/8/15

Y1 - 2012/8/15

N2 - TRPM7 encodes a Ca2+-permeable nonselective cation channel with kinase activity. TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been established. Here we report that high levels of TRPM7 expression independently predict poor outcome in breast cancer patients and that it is functionally required for metastasis formation in a mouse xenograft model of human breast cancer. Mechanistic investigation revealed that TRPM7 regulated myosin II-based cellular tension, thereby modifying focal adhesion number, cell-cell adhesion and polarized cell movement. Our findings therefore suggest that TRPM7 is part of a mechanosensory complex adopted by cancer cells to drive metastasis formation.

AB - TRPM7 encodes a Ca2+-permeable nonselective cation channel with kinase activity. TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been established. Here we report that high levels of TRPM7 expression independently predict poor outcome in breast cancer patients and that it is functionally required for metastasis formation in a mouse xenograft model of human breast cancer. Mechanistic investigation revealed that TRPM7 regulated myosin II-based cellular tension, thereby modifying focal adhesion number, cell-cell adhesion and polarized cell movement. Our findings therefore suggest that TRPM7 is part of a mechanosensory complex adopted by cancer cells to drive metastasis formation.

KW - Animals

KW - Breast Neoplasms/genetics

KW - Cell Adhesion/physiology

KW - Cell Line, Tumor

KW - Cell Movement/physiology

KW - Cytoskeleton/drug effects

KW - Disease Progression

KW - Female

KW - Gene Knockdown Techniques

KW - Humans

KW - Mice

KW - Mice, Transgenic

KW - Neoplasm Metastasis

KW - Neoplasm Staging

KW - Protein Serine-Threonine Kinases

KW - RNA, Messenger/biosynthesis

KW - Receptors, Estrogen/biosynthesis

KW - TRPM Cation Channels/biosynthesis

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U2 - 10.1158/0008-5472.CAN-11-3863

DO - 10.1158/0008-5472.CAN-11-3863

M3 - Article

C2 - 22871386

SN - 0008-5472

VL - 72

SP - 4250

EP - 4261

JO - Cancer research

JF - Cancer research

IS - 16

ER -

TRPM7 is required for breast tumor cell metastasis

Abstract

Keywords

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