GRB7 is required for triple-negative breast cancer cell invasion and survival

Orsi Giricz; Verónica Calvo; Stephanie C. Pero; David N. Krag; Joseph A. Sparano; Paraic A. Kenny

doi:10.1007/s10549-011-1822-6

GRB7 is required for triple-negative breast cancer cell invasion and survival

Orsi Giricz, Verónica Calvo, Stephanie C. Pero, David N. Krag, Joseph A. Sparano, Paraic A. Kenny

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

42 Scopus citations

Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous disease that is usually associated with poor prognosis, and frequently associated with the basal-like breast cancer gene expression profile. There are no targeted therapeutic modalities for this disease, and no useful bio-markers. High GRB7 RNA expression levels are associated with an elevated risk of recurrence in patients with operable TNBC treated with standard adjuvant anthracycline and taxane therapy. To determine whether GRB7 is involved in the pathobiology of TNBC, we evaluated the biological effects of GRB7 inhibition in a panel of triple-negative cell lines=MDA-MB-468, MDA-MB-231, HCC70, and T4-2. We found GRB7 inhibition reduced cell motility and invasion of these cell lines and promoted cell death by apoptosis in 3D culture. These data suggest that GRB7 itself, or GRB7-dependent pathways, may prove to be important therapeutic targets in this disease.

Original language	English
Pages (from-to)	607-615
Number of pages	9
Journal	Breast Cancer Research and Treatment
Volume	133
Issue number	2
DOIs	https://doi.org/10.1007/s10549-011-1822-6
State	Published - Jun 2012
Externally published	Yes

Keywords

Adapter proteins
GRB7
Receptor tyrosine kinase signaling
Triple-negative breast cancer
Tumor cell invasion

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10.1007/s10549-011-1822-6

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title = "GRB7 is required for triple-negative breast cancer cell invasion and survival",

abstract = "Triple-negative breast cancer (TNBC) is a heterogeneous disease that is usually associated with poor prognosis, and frequently associated with the basal-like breast cancer gene expression profile. There are no targeted therapeutic modalities for this disease, and no useful bio-markers. High GRB7 RNA expression levels are associated with an elevated risk of recurrence in patients with operable TNBC treated with standard adjuvant anthracycline and taxane therapy. To determine whether GRB7 is involved in the pathobiology of TNBC, we evaluated the biological effects of GRB7 inhibition in a panel of triple-negative cell lines=MDA-MB-468, MDA-MB-231, HCC70, and T4-2. We found GRB7 inhibition reduced cell motility and invasion of these cell lines and promoted cell death by apoptosis in 3D culture. These data suggest that GRB7 itself, or GRB7-dependent pathways, may prove to be important therapeutic targets in this disease.",

keywords = "Adapter proteins, GRB7, Receptor tyrosine kinase signaling, Triple-negative breast cancer, Tumor cell invasion",

author = "Orsi Giricz and Ver{\'o}nica Calvo and Pero, {Stephanie C.} and Krag, {David N.} and Sparano, {Joseph A.} and Kenny, {Paraic A.}",

note = "Funding Information: Acknowledgments OG and PK were supported by a postdoctoral fellowship (KG091136) and a Career Catalyst Award (KG100888) from the Susan G. Komen for the Cure Foundation. VC was supported by a postdoctoral fellowship from the Fundacion Alfonso Martin Escudero. SP and DK were supported by The National Cancer Institute (R01 CA80790) and in part by the SD Ireland Cancer Research Foundation. We gratefully acknowledge the Integrative Cancer Biology Program of the National Cancer Institute for provision of cell lines from the ICBP45 kit for use in this study.",

year = "2012",

month = jun,

doi = "10.1007/s10549-011-1822-6",

language = "English",

volume = "133",

pages = "607--615",

journal = "Breast Cancer Research and Treatment",

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T1 - GRB7 is required for triple-negative breast cancer cell invasion and survival

AU - Giricz, Orsi

AU - Calvo, Verónica

AU - Pero, Stephanie C.

AU - Krag, David N.

AU - Sparano, Joseph A.

AU - Kenny, Paraic A.

N1 - Funding Information: Acknowledgments OG and PK were supported by a postdoctoral fellowship (KG091136) and a Career Catalyst Award (KG100888) from the Susan G. Komen for the Cure Foundation. VC was supported by a postdoctoral fellowship from the Fundacion Alfonso Martin Escudero. SP and DK were supported by The National Cancer Institute (R01 CA80790) and in part by the SD Ireland Cancer Research Foundation. We gratefully acknowledge the Integrative Cancer Biology Program of the National Cancer Institute for provision of cell lines from the ICBP45 kit for use in this study.

PY - 2012/6

Y1 - 2012/6

N2 - Triple-negative breast cancer (TNBC) is a heterogeneous disease that is usually associated with poor prognosis, and frequently associated with the basal-like breast cancer gene expression profile. There are no targeted therapeutic modalities for this disease, and no useful bio-markers. High GRB7 RNA expression levels are associated with an elevated risk of recurrence in patients with operable TNBC treated with standard adjuvant anthracycline and taxane therapy. To determine whether GRB7 is involved in the pathobiology of TNBC, we evaluated the biological effects of GRB7 inhibition in a panel of triple-negative cell lines=MDA-MB-468, MDA-MB-231, HCC70, and T4-2. We found GRB7 inhibition reduced cell motility and invasion of these cell lines and promoted cell death by apoptosis in 3D culture. These data suggest that GRB7 itself, or GRB7-dependent pathways, may prove to be important therapeutic targets in this disease.

AB - Triple-negative breast cancer (TNBC) is a heterogeneous disease that is usually associated with poor prognosis, and frequently associated with the basal-like breast cancer gene expression profile. There are no targeted therapeutic modalities for this disease, and no useful bio-markers. High GRB7 RNA expression levels are associated with an elevated risk of recurrence in patients with operable TNBC treated with standard adjuvant anthracycline and taxane therapy. To determine whether GRB7 is involved in the pathobiology of TNBC, we evaluated the biological effects of GRB7 inhibition in a panel of triple-negative cell lines=MDA-MB-468, MDA-MB-231, HCC70, and T4-2. We found GRB7 inhibition reduced cell motility and invasion of these cell lines and promoted cell death by apoptosis in 3D culture. These data suggest that GRB7 itself, or GRB7-dependent pathways, may prove to be important therapeutic targets in this disease.

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KW - Receptor tyrosine kinase signaling

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GRB7 is required for triple-negative breast cancer cell invasion and survival

Abstract

Keywords

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