Comparative proteomic profiling of triple-negative breast cancer reveals that up-regulation of RhoGDI-2 is associated to the inhibition of caspase 3 and caspase 9

Marcos A. Muñiz Lino, Yadira Palacios-Rodríguez, Sergio Rodríguez-Cuevas, Verónica Bautista-Piña, Laurence A. Marchat, Erika Ruíz-García, Horacio Astudillo-de la Vega, Ana E. González-Santiago, Ali Flores-Pérez, José Díaz-Chávez, Ángeles Carlos-Reyes, Elizbeth Álvarez-Sánchez, César López-Camarillo

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Abstract

© 2014 Elsevier B.V. There are no targeted therapeutic modalities for triple-negative breast cancer (TNBC), thus it is associated with poor prognosis and worst clinical outcome. Here, our aim was to identify deregulated proteins in TNBC with potential therapeutic applications. Proteomics profiling of TNBC and normal breast tissues through two-dimensional electrophoresis and ESI-MS/MS mass spectrometry revealed the existence of 16 proteins (RhoGDI-2, HSP27, SOD1, DJ1, UBE2N, PSME1, FTL, SH3BGRL, and eIF5A-1) with increased abundance in carcinomas. We also evidenced for the first time the deregulation of COX5, MTPN and DB1 proteins in TNBC that may represent novel tumor markers. Particularly, we confirmed the overexpression of the Rho-GDP dissociation inhibitor 2 (RhoGDI-2) in distinct breast cancer subtypes, as well as in metastatic cell lines derived from lung, prostate, and breast cancer. Remarkably, targeted disruption of RhoGDI-2 by RNA interference induced mitochondrial dysfunction, and facilitated caspase-3 and -9 activation in two breast cancer cell lines. Moreover, suppression of RhoGDI-2 resulted in a robust sensitization of breast cancer cells to cisplatin therapy. In conclusion, we identified novel proteins deregulated in TNBC, and confirmed the overexpression of RhoGDI-2. We propose that RhoGDI-2 inhibition may be exploited as a potential therapeutic strategy along cisplatin-based chemotherapy in breast cancer. Biological significance: There are no useful biomarkers neither targeted therapeutic modalities for triple-negative breast cancer, which highly contributes to the poor prognosis of this breast cancer subtype. In this work, we used two-dimensional electrophoresis and ESI-MS/MS spectrometry to identify novel deregulated proteins in breast cancer tissues. Particularly, our results showed that RhoGDI-2, a protein that has been associated to metastasis and poor survival in human cancers, is overexpressed in different subtypes of breast tumors, as well as in metastatic cell lines derived from lung, prostate, and breast cancer. Our data also provided novel insights about the role of RhoGDI-2 in apoptosis through intrinsic pathway inhibition. Importantly, they suggested that targeted modulation of RhoGDI-2 levels might be a useful strategy for breast cancer therapy.This article is part of a Special Issue entitled: Proteomics, mass spectrometry and peptidomics, Cancun 2013. Guest Editors: César López-Camarillo, Victoria Pando-Robles and Bronwyn Jane Barkla.
Original languageAmerican English
Pages (from-to)198-211
Number of pages176
JournalJournal of Proteomics
DOIs
StatePublished - 5 Dec 2014

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rho Guanine Nucleotide Dissociation Inhibitor beta
Triple Negative Breast Neoplasms
Caspase 9
Caspase 3
Proteomics
Up-Regulation
Breast Neoplasms
Cells
Proteins
Electrophoresis
Cisplatin
Mass spectrometry
Cell Line
Tissue
Lung Neoplasms
Mass Spectrometry
Prostatic Neoplasms
Therapeutics
Chemotherapy
Deregulation

Cite this

Muñiz Lino, Marcos A. ; Palacios-Rodríguez, Yadira ; Rodríguez-Cuevas, Sergio ; Bautista-Piña, Verónica ; Marchat, Laurence A. ; Ruíz-García, Erika ; Astudillo-de la Vega, Horacio ; González-Santiago, Ana E. ; Flores-Pérez, Ali ; Díaz-Chávez, José ; Carlos-Reyes, Ángeles ; Álvarez-Sánchez, Elizbeth ; López-Camarillo, César. / Comparative proteomic profiling of triple-negative breast cancer reveals that up-regulation of RhoGDI-2 is associated to the inhibition of caspase 3 and caspase 9. In: Journal of Proteomics. 2014 ; pp. 198-211.
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abstract = "{\circledC} 2014 Elsevier B.V. There are no targeted therapeutic modalities for triple-negative breast cancer (TNBC), thus it is associated with poor prognosis and worst clinical outcome. Here, our aim was to identify deregulated proteins in TNBC with potential therapeutic applications. Proteomics profiling of TNBC and normal breast tissues through two-dimensional electrophoresis and ESI-MS/MS mass spectrometry revealed the existence of 16 proteins (RhoGDI-2, HSP27, SOD1, DJ1, UBE2N, PSME1, FTL, SH3BGRL, and eIF5A-1) with increased abundance in carcinomas. We also evidenced for the first time the deregulation of COX5, MTPN and DB1 proteins in TNBC that may represent novel tumor markers. Particularly, we confirmed the overexpression of the Rho-GDP dissociation inhibitor 2 (RhoGDI-2) in distinct breast cancer subtypes, as well as in metastatic cell lines derived from lung, prostate, and breast cancer. Remarkably, targeted disruption of RhoGDI-2 by RNA interference induced mitochondrial dysfunction, and facilitated caspase-3 and -9 activation in two breast cancer cell lines. Moreover, suppression of RhoGDI-2 resulted in a robust sensitization of breast cancer cells to cisplatin therapy. In conclusion, we identified novel proteins deregulated in TNBC, and confirmed the overexpression of RhoGDI-2. We propose that RhoGDI-2 inhibition may be exploited as a potential therapeutic strategy along cisplatin-based chemotherapy in breast cancer. Biological significance: There are no useful biomarkers neither targeted therapeutic modalities for triple-negative breast cancer, which highly contributes to the poor prognosis of this breast cancer subtype. In this work, we used two-dimensional electrophoresis and ESI-MS/MS spectrometry to identify novel deregulated proteins in breast cancer tissues. Particularly, our results showed that RhoGDI-2, a protein that has been associated to metastasis and poor survival in human cancers, is overexpressed in different subtypes of breast tumors, as well as in metastatic cell lines derived from lung, prostate, and breast cancer. Our data also provided novel insights about the role of RhoGDI-2 in apoptosis through intrinsic pathway inhibition. Importantly, they suggested that targeted modulation of RhoGDI-2 levels might be a useful strategy for breast cancer therapy.This article is part of a Special Issue entitled: Proteomics, mass spectrometry and peptidomics, Cancun 2013. Guest Editors: C{\'e}sar L{\'o}pez-Camarillo, Victoria Pando-Robles and Bronwyn Jane Barkla.",
author = "{Mu{\~n}iz Lino}, {Marcos A.} and Yadira Palacios-Rodr{\'i}guez and Sergio Rodr{\'i}guez-Cuevas and Ver{\'o}nica Bautista-Pi{\~n}a and Marchat, {Laurence A.} and Erika Ru{\'i}z-Garc{\'i}a and {Astudillo-de la Vega}, Horacio and Gonz{\'a}lez-Santiago, {Ana E.} and Ali Flores-P{\'e}rez and Jos{\'e} D{\'i}az-Ch{\'a}vez and {\'A}ngeles Carlos-Reyes and Elizbeth {\'A}lvarez-S{\'a}nchez and C{\'e}sar L{\'o}pez-Camarillo",
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doi = "10.1016/j.jprot.2014.04.019",
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Muñiz Lino, MA, Palacios-Rodríguez, Y, Rodríguez-Cuevas, S, Bautista-Piña, V, Marchat, LA, Ruíz-García, E, Astudillo-de la Vega, H, González-Santiago, AE, Flores-Pérez, A, Díaz-Chávez, J, Carlos-Reyes, Á, Álvarez-Sánchez, E & López-Camarillo, C 2014, 'Comparative proteomic profiling of triple-negative breast cancer reveals that up-regulation of RhoGDI-2 is associated to the inhibition of caspase 3 and caspase 9', Journal of Proteomics, pp. 198-211. https://doi.org/10.1016/j.jprot.2014.04.019

Comparative proteomic profiling of triple-negative breast cancer reveals that up-regulation of RhoGDI-2 is associated to the inhibition of caspase 3 and caspase 9. / Muñiz Lino, Marcos A.; Palacios-Rodríguez, Yadira; Rodríguez-Cuevas, Sergio; Bautista-Piña, Verónica; Marchat, Laurence A.; Ruíz-García, Erika; Astudillo-de la Vega, Horacio; González-Santiago, Ana E.; Flores-Pérez, Ali; Díaz-Chávez, José; Carlos-Reyes, Ángeles; Álvarez-Sánchez, Elizbeth; López-Camarillo, César.

In: Journal of Proteomics, 05.12.2014, p. 198-211.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Comparative proteomic profiling of triple-negative breast cancer reveals that up-regulation of RhoGDI-2 is associated to the inhibition of caspase 3 and caspase 9

AU - Muñiz Lino, Marcos A.

AU - Palacios-Rodríguez, Yadira

AU - Rodríguez-Cuevas, Sergio

AU - Bautista-Piña, Verónica

AU - Marchat, Laurence A.

AU - Ruíz-García, Erika

AU - Astudillo-de la Vega, Horacio

AU - González-Santiago, Ana E.

AU - Flores-Pérez, Ali

AU - Díaz-Chávez, José

AU - Carlos-Reyes, Ángeles

AU - Álvarez-Sánchez, Elizbeth

AU - López-Camarillo, César

PY - 2014/12/5

Y1 - 2014/12/5

N2 - © 2014 Elsevier B.V. There are no targeted therapeutic modalities for triple-negative breast cancer (TNBC), thus it is associated with poor prognosis and worst clinical outcome. Here, our aim was to identify deregulated proteins in TNBC with potential therapeutic applications. Proteomics profiling of TNBC and normal breast tissues through two-dimensional electrophoresis and ESI-MS/MS mass spectrometry revealed the existence of 16 proteins (RhoGDI-2, HSP27, SOD1, DJ1, UBE2N, PSME1, FTL, SH3BGRL, and eIF5A-1) with increased abundance in carcinomas. We also evidenced for the first time the deregulation of COX5, MTPN and DB1 proteins in TNBC that may represent novel tumor markers. Particularly, we confirmed the overexpression of the Rho-GDP dissociation inhibitor 2 (RhoGDI-2) in distinct breast cancer subtypes, as well as in metastatic cell lines derived from lung, prostate, and breast cancer. Remarkably, targeted disruption of RhoGDI-2 by RNA interference induced mitochondrial dysfunction, and facilitated caspase-3 and -9 activation in two breast cancer cell lines. Moreover, suppression of RhoGDI-2 resulted in a robust sensitization of breast cancer cells to cisplatin therapy. In conclusion, we identified novel proteins deregulated in TNBC, and confirmed the overexpression of RhoGDI-2. We propose that RhoGDI-2 inhibition may be exploited as a potential therapeutic strategy along cisplatin-based chemotherapy in breast cancer. Biological significance: There are no useful biomarkers neither targeted therapeutic modalities for triple-negative breast cancer, which highly contributes to the poor prognosis of this breast cancer subtype. In this work, we used two-dimensional electrophoresis and ESI-MS/MS spectrometry to identify novel deregulated proteins in breast cancer tissues. Particularly, our results showed that RhoGDI-2, a protein that has been associated to metastasis and poor survival in human cancers, is overexpressed in different subtypes of breast tumors, as well as in metastatic cell lines derived from lung, prostate, and breast cancer. Our data also provided novel insights about the role of RhoGDI-2 in apoptosis through intrinsic pathway inhibition. Importantly, they suggested that targeted modulation of RhoGDI-2 levels might be a useful strategy for breast cancer therapy.This article is part of a Special Issue entitled: Proteomics, mass spectrometry and peptidomics, Cancun 2013. Guest Editors: César López-Camarillo, Victoria Pando-Robles and Bronwyn Jane Barkla.

AB - © 2014 Elsevier B.V. There are no targeted therapeutic modalities for triple-negative breast cancer (TNBC), thus it is associated with poor prognosis and worst clinical outcome. Here, our aim was to identify deregulated proteins in TNBC with potential therapeutic applications. Proteomics profiling of TNBC and normal breast tissues through two-dimensional electrophoresis and ESI-MS/MS mass spectrometry revealed the existence of 16 proteins (RhoGDI-2, HSP27, SOD1, DJ1, UBE2N, PSME1, FTL, SH3BGRL, and eIF5A-1) with increased abundance in carcinomas. We also evidenced for the first time the deregulation of COX5, MTPN and DB1 proteins in TNBC that may represent novel tumor markers. Particularly, we confirmed the overexpression of the Rho-GDP dissociation inhibitor 2 (RhoGDI-2) in distinct breast cancer subtypes, as well as in metastatic cell lines derived from lung, prostate, and breast cancer. Remarkably, targeted disruption of RhoGDI-2 by RNA interference induced mitochondrial dysfunction, and facilitated caspase-3 and -9 activation in two breast cancer cell lines. Moreover, suppression of RhoGDI-2 resulted in a robust sensitization of breast cancer cells to cisplatin therapy. In conclusion, we identified novel proteins deregulated in TNBC, and confirmed the overexpression of RhoGDI-2. We propose that RhoGDI-2 inhibition may be exploited as a potential therapeutic strategy along cisplatin-based chemotherapy in breast cancer. Biological significance: There are no useful biomarkers neither targeted therapeutic modalities for triple-negative breast cancer, which highly contributes to the poor prognosis of this breast cancer subtype. In this work, we used two-dimensional electrophoresis and ESI-MS/MS spectrometry to identify novel deregulated proteins in breast cancer tissues. Particularly, our results showed that RhoGDI-2, a protein that has been associated to metastasis and poor survival in human cancers, is overexpressed in different subtypes of breast tumors, as well as in metastatic cell lines derived from lung, prostate, and breast cancer. Our data also provided novel insights about the role of RhoGDI-2 in apoptosis through intrinsic pathway inhibition. Importantly, they suggested that targeted modulation of RhoGDI-2 levels might be a useful strategy for breast cancer therapy.This article is part of a Special Issue entitled: Proteomics, mass spectrometry and peptidomics, Cancun 2013. Guest Editors: César López-Camarillo, Victoria Pando-Robles and Bronwyn Jane Barkla.

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