Rhamm is a multifunctional protein that regulates cancer progression

Britney J. Messam, Cornelia Tolg, James B. McCarthy, Andrew C. Nelson, Eva A. Turley

Research output: Contribution to journalReview articlepeer-review


The functional complexity of higher organisms is not easily accounted for by the size of their genomes. Rather, complexity appears to be generated by transcriptional, translational, and post-translational mechanisms and tissue organization that produces a context-dependent response of cells to specific stimuli. One property of gene products that likely increases the ability of cells to respond to stimuli with complexity is the multifunctionality of expressed proteins. Receptor for hy-aluronan-mediated motility (RHAMM) is an example of a multifunctional protein that controls differential responses of cells in response-to-injury contexts. Here, we trace its evolution into a sensor-transducer of tissue injury signals in higher organisms through the detection of hyaluronan (HA) that accumulates in injured microenvironments. Our goal is to highlight the domain and isoform structures that generate RHAMM’s function complexity and model approaches for targeting its key functions to control cancer progression.

Original languageEnglish (US)
Article number10313
JournalInternational journal of molecular sciences
Issue number19
StatePublished - Oct 1 2021

Bibliographical note

Funding Information:
B.J.M. is supported by the Translational Breast Cancer Research Scholarship academic award funded by the Breast Cancer Society of Canada. Acknowledgments: Figures 7 and 8 in this paper were created using BioRender.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


  • Cancer
  • Domains
  • Evolution
  • HA
  • Isoforms
  • Multi-functions
  • Signaling

PubMed: MeSH publication types

  • Journal Article
  • Review


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