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Integrin Signaling Shaping BTK-Inhibitor Resistance
Integrins are adhesion molecules that function as anchors in retaining tumor cells in supportive tissues and facilitating metastasis. Beta1 integrins are known to contribute to cell adhesion-mediated drug resistance in cancer. Very late antigen-4 (VLA-4), a CD49d/CD29 heterodimer, is a beta1 integri...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322986/ https://www.ncbi.nlm.nih.gov/pubmed/35883678 http://dx.doi.org/10.3390/cells11142235 |
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author | Polcik, Laura Dannewitz Prosseda, Svenja Pozzo, Federico Zucchetto, Antonella Gattei, Valter Hartmann, Tanja Nicole |
author_facet | Polcik, Laura Dannewitz Prosseda, Svenja Pozzo, Federico Zucchetto, Antonella Gattei, Valter Hartmann, Tanja Nicole |
author_sort | Polcik, Laura |
collection | PubMed |
description | Integrins are adhesion molecules that function as anchors in retaining tumor cells in supportive tissues and facilitating metastasis. Beta1 integrins are known to contribute to cell adhesion-mediated drug resistance in cancer. Very late antigen-4 (VLA-4), a CD49d/CD29 heterodimer, is a beta1 integrin implicated in therapy resistance in both solid tumors and haematological malignancies such as chronic lymphocytic leukemia (CLL). A complex inside-out signaling mechanism activates VLA-4, which might include several therapeutic targets for CLL. Treatment regimens for this disease have recently shifted towards novel agents targeting BCR signaling. Bruton’s tyrosine kinase (BTK) is a component of B cell receptor signaling and BTK inhibitors such as ibrutinib are highly successful; however, their limitations include indefinite drug administration, the development of therapy resistance, and toxicities. VLA-4 might be activated independently of BTK, resulting in an ongoing interaction of CD49d-expressing leukemic cells with their surrounding tissue, which may reduce the success of therapy with BTK inhibitors and increases the need for alternative therapies. In this context, we discuss the inside-out signaling cascade culminating in VLA-4 activation, consider the advantages and disadvantages of BTK inhibitors in CLL and elucidate the mechanisms behind cell adhesion-mediated drug resistance. |
format | Online Article Text |
id | pubmed-9322986 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93229862022-07-27 Integrin Signaling Shaping BTK-Inhibitor Resistance Polcik, Laura Dannewitz Prosseda, Svenja Pozzo, Federico Zucchetto, Antonella Gattei, Valter Hartmann, Tanja Nicole Cells Review Integrins are adhesion molecules that function as anchors in retaining tumor cells in supportive tissues and facilitating metastasis. Beta1 integrins are known to contribute to cell adhesion-mediated drug resistance in cancer. Very late antigen-4 (VLA-4), a CD49d/CD29 heterodimer, is a beta1 integrin implicated in therapy resistance in both solid tumors and haematological malignancies such as chronic lymphocytic leukemia (CLL). A complex inside-out signaling mechanism activates VLA-4, which might include several therapeutic targets for CLL. Treatment regimens for this disease have recently shifted towards novel agents targeting BCR signaling. Bruton’s tyrosine kinase (BTK) is a component of B cell receptor signaling and BTK inhibitors such as ibrutinib are highly successful; however, their limitations include indefinite drug administration, the development of therapy resistance, and toxicities. VLA-4 might be activated independently of BTK, resulting in an ongoing interaction of CD49d-expressing leukemic cells with their surrounding tissue, which may reduce the success of therapy with BTK inhibitors and increases the need for alternative therapies. In this context, we discuss the inside-out signaling cascade culminating in VLA-4 activation, consider the advantages and disadvantages of BTK inhibitors in CLL and elucidate the mechanisms behind cell adhesion-mediated drug resistance. MDPI 2022-07-18 /pmc/articles/PMC9322986/ /pubmed/35883678 http://dx.doi.org/10.3390/cells11142235 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Polcik, Laura Dannewitz Prosseda, Svenja Pozzo, Federico Zucchetto, Antonella Gattei, Valter Hartmann, Tanja Nicole Integrin Signaling Shaping BTK-Inhibitor Resistance |
title | Integrin Signaling Shaping BTK-Inhibitor Resistance |
title_full | Integrin Signaling Shaping BTK-Inhibitor Resistance |
title_fullStr | Integrin Signaling Shaping BTK-Inhibitor Resistance |
title_full_unstemmed | Integrin Signaling Shaping BTK-Inhibitor Resistance |
title_short | Integrin Signaling Shaping BTK-Inhibitor Resistance |
title_sort | integrin signaling shaping btk-inhibitor resistance |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322986/ https://www.ncbi.nlm.nih.gov/pubmed/35883678 http://dx.doi.org/10.3390/cells11142235 |
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