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RHAMM Is a Multifunctional Protein That Regulates Cancer Progression

期刊

出版社

MDPI
DOI: 10.3390/ijms221910313

关键词

RHAMM; HA; signaling; domains; isoforms; evolution; cancer; multi-functions

资金

  1. Translational Breast Cancer Research Scholarship academic award - Breast Cancer Society of Canada
  2. Breast Cancer Society of Canada
  3. LRCP catalyst
  4. WSS CIHR Seed Grant
  5. Atwater Fund
  6. Elsa Pardee and Chairman's Fund Professor in Cancer Research
  7. American Cancer Society [132574-CSDG-18139-01-CSM]

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The functional complexity of higher organisms is generated by transcriptional, translational, and post-translational mechanisms, as well as tissue organization. Multifunctionality of expressed proteins helps cells respond to stimuli. RHAMM is a multifunctional protein that controls differential responses of cells in injury contexts and evolved into a sensor-transducer in higher organisms.
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 hyaluronan-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.

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