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Review
. 2016 Mar 23;5(4):39.
doi: 10.3390/jcm5040039.

Osteopontin-A Master Regulator of Epithelial-Mesenchymal Transition

Anai N Kothari  1   2 , Matthew L Arffa  3 , Victor Chang  4 , Robert H Blackwell  5 , Wing-Kin Syn  6 , Jiwang Zhang  7 , Zhiyong Mi  8 , Paul C Kuo  9
Affiliations
Review

Osteopontin-A Master Regulator of Epithelial-Mesenchymal Transition

Anai N Kothari et al. J Clin Med. .

Abstract

Osteopontin (OPN) plays an important functional role in both physiologic and pathologic states. OPN is implicated in the progression of fibrosis, cancer, and metastatic disease in several organ systems. The epithelial-mesenchymal transition (EMT), first described in embryology, is increasingly being recognized as a significant contributor to fibrotic phenotypes and tumor progression. Several well-established transcription factors regulate EMT and are conserved across tissue types and organ systems, including TWIST, zinc finger E-box-binding homeobox (ZEB), and SNAIL-family members. Recent literature points to an important relationship between OPN and EMT, implicating OPN as a key regulatory component of EMT programs. In this review, OPN's interplay with traditional EMT activators, both directly and indirectly, will be discussed. Also, OPN's ability to restructure the tissue and tumor microenvironment to indirectly modify EMT will be reviewed. Together, these diverse pathways demonstrate that OPN is able to modulate EMT and provide new targets for directing therapeutics.

Keywords: cancer-associated fibroblasts; epithelial-mesenchymal transition; fibrosis; osteopontin; tumor metastasis; tumor microenvironment.

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Figures

Figure 1
Figure 1
The appearance of “osteopontin” and epithelial-mesenchymal transition in the same peer-reviewed scientific article over time (per year), beginning in 2007. Data on number of articles obtained using Google Scholar search with terms “osteopontin (OPN) + epithelial-mesenchymal transition (EMT)” vs. “EMT” only, excluding patents and citations.
Figure 2
Figure 2
Overview of key EMT pathways regulated by osteopontin directly and indirectly. (A) Regulation of TWIST and EMT by OPN; (B) Regulation of zinc finger E-box-binding homeobox (ZEB) and EMT by OPN; (C) Regulation of SNAIL and EMT by OPN.
Figure 3
Figure 3
Microenvironmental regulation of EMT by OPN-mediated activation of stromal elements.
See this image and copyright information in PMC

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