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. 2019 Aug 20;9:12124. doi: 10.1038/s41598-019-48420-w

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Both Daple-fl and Daple-V2 isoforms are downregulated during adenoma-to-carcinoma conversion. (A,B) Expression of Daple protein was analyzed in formalin-fixed paraffin embedded human tissues (normal, adenomas and carcinomas) by immunohistochemistry (IHC) using anti-Daple-CT antibody that can detect both Daple-fl and Daple-V2 isoforms. Left: Representative tissues from each stained category are shown. Brown = positive stain. Right: Bar graphs display the proportion of samples in each category that stained positive vs. negative. (C) Schematic summarizing profile of expression of Daple-fl and Daple-V2 isoforms during cancer initiation and metastatic progression in the colon. Upper: Various steps and histopathological stages of colorectal cancer progression are shown. Major genetic mutations/ deletions of key genes that herald the step-wise progression are indicated. Daple (both Daple-fl and Daple-V2) are decreased during adenoma to carcinoma progression (red box). Later, during cancer progression and systemic dissemination, total levels of Daple go up (green box), largely owing to an upregulation of its full-length (Daple-fl) transcript. Lower: Changes in the profile of expression of both Daple isoforms (Daple V2 = green; Daple-fl = purple) and their relationship to the previously identified patterns of non-canonical Wnt signaling (gray) is shown.