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. 2021 Mar 27;13(7):1548. doi: 10.3390/cancers13071548

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Immunostaining of β-catenin, MMP-14 (MT-MMP1), pp42-44 (pERK1/2), and p21 in WT DEN and hSDC1^+/+ DEN livers at month 3. In hSDC1^+/+ DEN livers with retained structure and devoid of premalignant foci, β-catenin was localized exclusively to the cell surface of hepatocytes. In the preneoplastic foci of WT DEN livers, polymorphic cells already displayed nuclear β-catenin positivity. In the same foci, strong immunostaining of MMP14, a metalloprotease known to be implicated in SDC1 shedding, was seen on cell surfaces, whereas only perisinusoidal cells but no normal hepatocytes expressed MMP14 in hSDC1^+/+ DEN livers. In WT DEN livers, preneoplastic foci were extensively marked by pp42-44 positivity, whereas only small islets of cells displayed high pERK1/2 in hSDC1^+/+ DEN. Areas with high pERK1/2 exhibited concomitant activation of the cyclin-dependent kinase inhibitor p21. White arrows show the nuclear β-catenin in the tumor area. Images are at 200× magnification, scale bar: 50 μm.