Differential roles of protease isoforms in the tumor microenvironment

  • Chamikara Liyanage
  • Achala Fernando
  • Jyotsna BatraEmail author


Alternative splicing of precursor mRNA is a key mediator of gene expression regulation leading to greater diversity of the proteome in complex organisms. Systematic sequencing of the human genome and transcriptome has led to our understanding of how alternative splicing of critical genes leads to multiple pathological conditions such as cancer. For many years, proteases were known only for their roles as proteolytic enzymes, acting to regulate/process proteins associated with diverse cellular functions. However, the differential expression and altered function of various protease isoforms, such as (i) anti-apoptotic activities, (ii) mediating intercellular adhesion, and (iii) modifying the extracellular matrix, are evidence of their specific contribution towards shaping the tumor microenvironment. Revealing the alternative splicing of protease genes and characterization of their protein products/isoforms with distinct and opposing functions creates a platform to understand how protease isoforms contribute to specific cancer hallmarks. Here, in this review, we address cancer-specific isoforms produced by the alternative splicing of proteases and their distinctive roles in the tumor microenvironment.


Protease Alternative splicing Cancer Tumor microenvironment 


Funding information

Chamikara Liyanage and Achala Fernando acknowledge QUT Postgraduate Research Award (QUTPRA) and QUT HDR Tuition Fee Sponsorship; Jyotsna Batra acknowledges Cancer Council Australia, Cure Cancer and Cancer Australia PdCCRS Young Investigator and a National Health and Medical Research Council (NHMRC) Career Development Fellowship.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical InnovationQueensland University of TechnologyBrisbaneAustralia
  2. 2.Australian Prostate Cancer Research Centre-Queensland (APCRC-Q), Translational Research InstituteQueensland University of TechnologyBrisbaneAustralia

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