Evaluating nuclear translocation of surface receptors: recommendations arising from analysis of CD44

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 marker...

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Bibliographic Details
Published in:Histochemistry and cell biology 2020-02, Vol.153 (2), p.77-87
Main Authors: Thorne, Rick F., Wang, Yan, Zhang, Yan, Jing, Xueli, Zhang, Xu Dong, de Bock, Charles E., Oliveira, Camila S.
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
CD44 antigen
Cell Biology
Cell Nucleus - metabolism
Developmental Biology
Extracellular matrix
HT29 Cells
Humans
Hyaluronan Receptors - analysis
Hyaluronan Receptors - metabolism
Hyaluronic acid
Kinases
Metastases
Nuclear transport
Original Paper
Proteolysis
Receptors, Cell Surface - metabolism
Signal Transduction
Stem cells
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Summary: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.
ISSN:0948-6143
1432-119X
DOI:10.1007/s00418-019-01835-y