Clinical relevance of macromolecular complexes involving integrins, potassium and sodium ion channels and the sodium/proton antiporter in human breast cancer
Abstract Background Mounting evidence underline the relevance of macromolecular complexes in cancer. Integrins frequently recruit ion channels and transporters within complexes which behave as signaling hubs. A complex composed by β1 integrin, hERG1 K+ channel, the neonatal form of the Na+ channel N...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Cancer Cell International |
| Online Access: | https://doi.org/10.1186/s12935-025-03653-w |
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| author | Elena Lastraioli Jessica Iorio Francesco Piazza Chiara Capitani Michele Santillo Claudia Duranti Simonetta Bianchi Icro Meattini Scott P. Fraser Mustafa B. A. Djamgoz Andrea Becchetti Annarosa Arcangeli |
| author_facet | Elena Lastraioli Jessica Iorio Francesco Piazza Chiara Capitani Michele Santillo Claudia Duranti Simonetta Bianchi Icro Meattini Scott P. Fraser Mustafa B. A. Djamgoz Andrea Becchetti Annarosa Arcangeli |
| author_sort | Elena Lastraioli |
| collection | DOAJ |
| description | Abstract Background Mounting evidence underline the relevance of macromolecular complexes in cancer. Integrins frequently recruit ion channels and transporters within complexes which behave as signaling hubs. A complex composed by β1 integrin, hERG1 K+ channel, the neonatal form of the Na+ channel NaV 1.5 (nNaV1.5) and the Na+/H+ antiporter NHE1 (NHE1/hERG1/β1/nNaV1.5 complex) has been recently described to be expressed and regulate relevant cancer related behaviors in Breast Cancer (BCa) cells. Methods We analyzed the expression and impact on outcome of the genes encoding the four proteins forming the NHE1/hERG1/β1/nNaV1.5 complex (SLC9A1, KCNH2, ITGB1 and SCN5A) in public datasets. The corresponding proteins were also evaluated by immunohistochemistry and their expression was correlated with clinic-pathological and molecular characteristics and patients’ survival. Results The expression of KCNH2 and SCN5A was significantly correlated in primary BCa as occurs in the heart, although with a broader distribution, forming a functional network which also included ITGB1 and SLC9A1. The co-expression proteins emerged from the immunohistochemistry analysis. Interestingly, hERG1, nNav1.5 and the hERG1/β1 integrin complex associated with several clinical features, including molecular subtype and hormone receptor status. Moreover, hERG1 and the combination of hERG1 and nNav1.5 had impact on prognosis, contributing to identifying a group of patients with worse prognosis. Conclusions hERG1 and nNav1.5 channels along with β1 integrins and the NHE1 antiporter are co-expressed in BCa both at gene and protein levels, assembling into a macromolecular complex. The NHE1/hERG1/β1/nNaV1.5 complex can be considered a novel biomarker and potential target for therapy for BCa patients. |
| format | Article |
| id | doaj-art-b0f70ea11c154480a03f5320600dc132 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-b0f70ea11c154480a03f5320600dc1322025-01-26T12:53:32ZengBMCCancer Cell International1475-28672025-01-0125111910.1186/s12935-025-03653-wClinical relevance of macromolecular complexes involving integrins, potassium and sodium ion channels and the sodium/proton antiporter in human breast cancerElena Lastraioli0Jessica Iorio1Francesco Piazza2Chiara Capitani3Michele Santillo4Claudia Duranti5Simonetta Bianchi6Icro Meattini7Scott P. Fraser8Mustafa B. A. Djamgoz9Andrea Becchetti10Annarosa Arcangeli11Department of Experimental and Clinical Medicine, University of FlorenceDepartment of Experimental and Clinical Medicine, University of FlorenceCSDC (Center for the Study of complex dynamics), University of FlorenceDepartment of Experimental and Clinical Medicine, University of FlorenceDepartment of Experimental and Clinical Medicine, University of FlorenceDepartment of Experimental and Clinical Medicine, University of FlorenceDepartment of Health Sciences, Division of Pathological Anatomy, University of FlorenceDepartment of Experimental and Clinical Biomedical Sciences Mario Serio, University of FlorenceDepartment of Life Sciences, Imperial College LondonDepartment of Life Sciences, Imperial College LondonDepartment of Biotechnology and Biosciences, University of Milano BicoccaDepartment of Experimental and Clinical Medicine, University of FlorenceAbstract Background Mounting evidence underline the relevance of macromolecular complexes in cancer. Integrins frequently recruit ion channels and transporters within complexes which behave as signaling hubs. A complex composed by β1 integrin, hERG1 K+ channel, the neonatal form of the Na+ channel NaV 1.5 (nNaV1.5) and the Na+/H+ antiporter NHE1 (NHE1/hERG1/β1/nNaV1.5 complex) has been recently described to be expressed and regulate relevant cancer related behaviors in Breast Cancer (BCa) cells. Methods We analyzed the expression and impact on outcome of the genes encoding the four proteins forming the NHE1/hERG1/β1/nNaV1.5 complex (SLC9A1, KCNH2, ITGB1 and SCN5A) in public datasets. The corresponding proteins were also evaluated by immunohistochemistry and their expression was correlated with clinic-pathological and molecular characteristics and patients’ survival. Results The expression of KCNH2 and SCN5A was significantly correlated in primary BCa as occurs in the heart, although with a broader distribution, forming a functional network which also included ITGB1 and SLC9A1. The co-expression proteins emerged from the immunohistochemistry analysis. Interestingly, hERG1, nNav1.5 and the hERG1/β1 integrin complex associated with several clinical features, including molecular subtype and hormone receptor status. Moreover, hERG1 and the combination of hERG1 and nNav1.5 had impact on prognosis, contributing to identifying a group of patients with worse prognosis. Conclusions hERG1 and nNav1.5 channels along with β1 integrins and the NHE1 antiporter are co-expressed in BCa both at gene and protein levels, assembling into a macromolecular complex. The NHE1/hERG1/β1/nNaV1.5 complex can be considered a novel biomarker and potential target for therapy for BCa patients.https://doi.org/10.1186/s12935-025-03653-w |
| spellingShingle | Elena Lastraioli Jessica Iorio Francesco Piazza Chiara Capitani Michele Santillo Claudia Duranti Simonetta Bianchi Icro Meattini Scott P. Fraser Mustafa B. A. Djamgoz Andrea Becchetti Annarosa Arcangeli Clinical relevance of macromolecular complexes involving integrins, potassium and sodium ion channels and the sodium/proton antiporter in human breast cancer Cancer Cell International |
| title | Clinical relevance of macromolecular complexes involving integrins, potassium and sodium ion channels and the sodium/proton antiporter in human breast cancer |
| title_full | Clinical relevance of macromolecular complexes involving integrins, potassium and sodium ion channels and the sodium/proton antiporter in human breast cancer |
| title_fullStr | Clinical relevance of macromolecular complexes involving integrins, potassium and sodium ion channels and the sodium/proton antiporter in human breast cancer |
| title_full_unstemmed | Clinical relevance of macromolecular complexes involving integrins, potassium and sodium ion channels and the sodium/proton antiporter in human breast cancer |
| title_short | Clinical relevance of macromolecular complexes involving integrins, potassium and sodium ion channels and the sodium/proton antiporter in human breast cancer |
| title_sort | clinical relevance of macromolecular complexes involving integrins potassium and sodium ion channels and the sodium proton antiporter in human breast cancer |
| url | https://doi.org/10.1186/s12935-025-03653-w |
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