Unexpected gain of function for the scaffolding protein plectin due to mislocalization in pancreatic cancer.
We recently demonstrated that plectin is a robust biomarker for pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive malignancies. In normal physiology, plectin is an intracellular scaffolding protein, but we have demonstrated localization on the extracellular surface of PDAC cells. In this study, we confirmed cell surface localization. Interestingly, we found that plectin cell surface localization was attributable to its presence in exosomes secreted from PDAC cells, which is dependent on the expression of integrin β4, a protein known to interact with cytosolic plectin. Moreover, plectin expression was necessary for efficient exosome production and was required to sustain enhanced tumor growth in immunodeficient and in immunocompetent mice. It is now clear that this PDAC biomarker plays a role in PDAC, and further understanding of plectin's contribution to PDAC could enable improved therapies.
Department of Biomedical Engineering, University of Virginia School of Engineering and Applied Sciences, Charlottesville, VA 22908.
Soo J
SJ
Shin
Jeffrey A
JA
Smith
Günther A
GA
Rezniczek
Sheng
S
Pan
Ru
R
Chen
Teresa A
TA
Brentnall
Gerhard
G
Wiche
Kimberly A
KA
Kelly
D000704:Analysis of Variance; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000503:physiopathology*; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D013058:Mass Spectrometry; D051379:Mice; D046529:Microscopy, Electron, Transmission; D051190:Plectin / Q000378:metabolism*; D040901:Proteomics
D017931:DNA Primers; C495332:PLEC protein, human; D051190:Plectin
invasion; migration; protein trafficking