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Tumor-stroma biomechanical crosstalk: a perspective on the role of caveolin-1 in tumor progression

Cancer and Metastasis Reviews volume 39, pages 485–503 (2020)Cite this article

Abstract

Tumor stiffening is a hallmark of malignancy that actively drives tumor progression and aggressiveness. Recent research has shed light onto several molecular underpinnings of this biomechanical process, which has a reciprocal crosstalk between tumor cells, stromal fibroblasts, and extracellular matrix remodeling at its core. This dynamic communication shapes the tumor microenvironment; significantly determines disease features including therapeutic resistance, relapse, or metastasis; and potentially holds the key for novel antitumor strategies. Caveolae and their components emerge as integrators of different aspects of cell function, mechanotransduction, and ECM–cell interaction. Here, we review our current knowledge on the several pivotal roles of the essential caveolar component caveolin-1 in this multidirectional biomechanical crosstalk and highlight standing questions in the field.

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Acknowledgments

We are grateful to the members of our laboratory and colleagues for useful discussions.

Funding

Research in our laboratory has been supported by grants from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO; SAF2011-25047, SAF2014-51876-R, SAF2017-83130-R, IGP-SO grant MINSEV1512-07-2016, CSD2009-0016 and BFU2016-81912-REDC), and the Worldwide Cancer Research Foundation (no. 15-0404) to M.A.d.P. M.A.d.P is also a member of the Tec4Bio consortium (ref. P2018/NMT­4443; “Actividades de I+D entre Grupos de Investigación en Tecnologías,” Comunidad Autónoma de Madrid/FEDER, Spain) and is co-recipient of grants from Fundació La Marató de TV3 (674/C/2013 and 201936). M.A.d.P’s group received funding from the European Union Horizon 2020 research and innovation programme under Marie Sklodowska-Curie grant agreement no. 641639 (BIOPOL ETN), of which V.J-J. was ESR trainee. M.S-A. was recipient of a CNIC IPP fellowship (COFUND programme 2014). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU), and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).

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  1. Fidel Nicolás Lolo, Víctor Jiménez-Jiménez and Miguel Sánchez-Álvarez contributed equally to this work.

Authors and Affiliations

  1. Mechanoadaptation and Caveolae Biology Lab, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain

    Fidel Nicolás Lolo, Víctor Jiménez-Jiménez, Miguel Sánchez-Álvarez & Miguel Ángel del Pozo

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  1. Fidel Nicolás Lolo
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  2. Víctor Jiménez-Jiménez
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Correspondence to Miguel Ángel del Pozo.

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Lolo, F.N., Jiménez-Jiménez, V., Sánchez-Álvarez, M. et al. Tumor-stroma biomechanical crosstalk: a perspective on the role of caveolin-1 in tumor progression. Cancer Metastasis Rev 39, 485–503 (2020). https://doi.org/10.1007/s10555-020-09900-y

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Keywords

  • Mechanobiology
  • Caveolae
  • Caveolin-1
  • Cancer
  • Stromal remodeling
  • Extracellular matrix (ECM)
  • Cancer-associated fibroblasts (CAFs)
  • YAP/TAZ
  • Integrin signaling
  • Cell contraction
  • Tumor cell reprogramming
  • Metastasis