Abstract:
:The vast majority of cancer deaths are caused by the formation of metastases rather than the primary tumor itself. Despite this clinical importance, the molecular and cellular events that support the dissemination of cancer cells are not yet fully unraveled. We have previously shown that CDX2, a homeotic transcription factor essential for gut development, acts as a colon-specific tumor suppressor and opposes metastasis. Here, using a combination of biochemical, biophysical, and immunofluorescence techniques, we further investigated the mechanisms promoted by CDX2 that might antagonize tumor cell dissemination. We found that CDX2 expression regulates the transcription of RHO GEFs, thereby activating RHO signaling cascades that lead to reorganization of the actin cytoskeleton and enhanced adherent junctions. Accordingly, we observed by atomic force microscopy (AFM) that colon cancer cells expressing CDX2 are less deformable, a feature that has been shown to correlate with poor metastatic potential. Thus, this study illustrates how the loss of expression of a transcription factor during colon cancer progression modifies the biomechanical characteristics of tumor cells and hence facilitates invasion and metastasis.
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Platet N,Hinkel I,Richert L,Murdamoothoo D,Moufok-Sadoun A,Vanier M,Lavalle P,Gaiddon C,Vautier D,Freund JN,Gross Idoi
10.1016/j.canlet.2016.10.040subject
Has Abstractpub_date
2017-02-01 00:00:00pages
57-64eissn
0304-3835issn
1872-7980pii
S0304-3835(16)30671-1journal_volume
386pub_type
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