University of Oulu

Rekad, Z., Izzi, V., Lamba, R., Ciais, D., & Van Obberghen-Schilling, E. (2022). The alternative matrisome: Alternative splicing of ECM proteins in development, homeostasis and tumor progression. Matrix Biology, 111, 26–52.

The alternative matrisome : alternative splicing of ECM proteins in development, homeostasis and tumor progression

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Author: Rekad, Zeinab1; Izzi, Valerio2,3,4; Lamba, Rijuta2,3;
Organizations: 1Université Côte d'Azur, CNRS, INSERM, iBV, Nice, France
2Faculty of Biochemistry and Molecular Medicine, University of Oulu, FI-90014 Oulu, Finland
3Faculty of Medicine, Research Unit of Biomedicine, University of Oulu, FI-90014 Oulu, Finland
4Finnish Cancer Institute, 00130 Helsinki, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 2.4 MB)
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Language: English
Published: Elsevier, 2022
Publish Date: 2022-07-06


The extracellular matrix (ECM) is a fundamental component of the tissue of multicellular organisms that is comprised of an intricate network of multidomain proteins and associated factors, collectively known as the matrisome. The ECM creates a biophysical environment that regulates essential cellular processes such as adhesion, proliferation and migration and impacts cell fate decisions. The composition of the ECM varies across organs, developmental stages and diseases. Interestingly, most ECM genes generate transcripts that undergo extensive alternative splicing events, producing multiple protein variants from one gene thus enhancing ECM complexity and impacting matrix architecture. Extensive studies over the past several decades have linked ECM remodeling and expression of alternatively spliced ECM isoforms to cancer, and reprogramming of the alternative splicing patterns in cells has recently been proposed as a new hallmark of tumor progression. Indeed, tumor-associated alternative splicing occurs in both malignant and non-malignant cells of the tumor environment and growing evidence suggests that expression of specific ECM splicing variants could be a key step for stromal activation. In this review, we present a general overview of alternative splicing mechanisms, featuring examples of ECM components. The importance of ECM variant expression during essential physiological processes, such as tissue organization and embryonic development is discussed as well as the dysregulation of alternative splicing in cancer. The overall aim of this review is to address the complexity of the ECM by highlighting the importance of the yet-to-be-fully-characterized “alternative” matrisome in physiological and pathological states such as cancer.

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Series: Matrix biology
ISSN: 0945-053X
ISSN-E: 1569-1802
ISSN-L: 0945-053X
Volume: 111
Pages: 26 - 52
DOI: 10.1016/j.matbio.2022.05.003
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: Support for this work was provided by the National Agency for Research (ANR-16-CE93-0005-01), the LabEx SIGNALIFE program (ANR11-LABX-0028-01), the Canceropôle Provence Alpes Côte d'Azur, Institut National du Cancer and Région Sud and the Université Côte d'Azur. EVO team members are affiliated to the Fédération Hospitalo-Universitaire OncoAge and EVO holds a Chair 3IA Côte d'Azur (ANR-19-P3IA-0002). This research is also connected to the DigiHealth-project, a strategic profiling project at the University of Oulu. The project is supported by the Academy of Finland (project number 326291), the University of Oulu, and the Finnish Cancer Institute, K. Albin Johansson Cancer Research Fellowship fund.
Copyright information: © 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http:/