- Title
- Evaluating nuclear translocation of surface receptors: recommendations arising from analysis of CD44
- Creator
- Thorne, Rick F.; Wang, Yan; Zhang, Yan; Jing, Xueli; Zhang, Xu Dong; de Bock, Charles E.; Oliveira, Camila S.
- Relation
- Histochemistry and Cell Biology Vol. 153, Issue 2, p. 77-87
- Publisher Link
- http://dx.doi.org/10.1007/s00418-019-01835-y
- Publisher
- Springer
- Resource Type
- journal article
- Date
- 2020
- Description
- CD44 is a transmembrane receptor that acts as adhesion protein, fundamentally recognizing hyaluronan, an essential component of the extracellular matrix. It has a well-established functional association with cancer metastasis, particularly the CD44 variant forms which are considered essential markers of cancer stem cells. CD44 itself lacks intrinsic kinase activity but rather engages in signalling through specific interactions with kinases and other signalling components. Proteolysis within its transmembrane region also leads to release of the CD44 cytoplasmic domain, which can translocate to the nucleus and regulate transcription. A third signalling modality has been reported where the intact CD44 receptor translocates to the nucleus. Here, we investigated the latter using imaging techniques together with biochemical analyses. Our findings support observations where CD44 is cleaved prior to nuclear translocation and challenges the evidence for the presence of intact CD44 receptors in the cell nucleus. Conclusions regarding the presence of intact CD44 in the cell nucleus as a signalling modality, therefore, require re-evaluation. We highlight artefacts and common technical issues associated with these experiments that can lead to misinterpretation.
- Subject
- CD44; nuclear translocation; signalling; regulated intramembranous proteolysis; intracellular domain; SDG 3; SDG 7; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1432377
- Identifier
- uon:39042
- Identifier
- ISSN:0948-6143
- Rights
- This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s00418-019-01835-y.
- Language
- eng
- Full Text
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