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β-catenin

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Journal Articles
Cancer Res (2022) 82 (4_Supplement): P4-01-09.
Published: 15 February 2022
... expression or phosphorylation with chemotherapy treatment inhibited the activity and expression of β-catenin. Importantly, a combination of WAVE3-deficiency and chemotherapy suppressed the oncogenic behavior of chemo-resistant TNBC cells, both in vitro and in vivo. This study suggests that a targeted...
Journal Articles
Cancer Res (2022) 82 (1): 60–74.
Published: 04 January 2022
... is a hallmark of cancer. Hyperactivation of Wnt/β-catenin signaling has been reported in hepatocellular carcinoma (HCC). However, the mechanisms inducing hyperactivation of Wnt/β-catenin signaling and strategies for targeting this pathway are incompletely understood. In this study, we find nucleoside...
Includes: Supplementary data
Journal Articles
Cancer Res (2021) 81 (13): 3554–3567.
Published: 01 July 2021
... that knockout of SETD2 in a c-MYC–driven PKD mouse model drove the transition to ccRCC. SETD2 inhibited β-catenin activity at transcriptional and posttranscriptional levels by competing with β-catenin for binding promoters of target genes and maintaining transcript levels of members of the β-catenin destruction...
Includes: Supplementary data
Journal Articles
Cancer Res (2021) 81 (13_Supplement): 3188.
Published: 01 July 2021
... cytokinesis in a subset of HM cells. Subsequent analyses suggested that this induction could be facilitated by direct cell-cell contact. We further identified that the cell-surface metadherin expression induced by β-catenin in HM cells is involved in this induction, while surface CEACAM1 expressed...
Journal Articles
Cancer Res (2021) 81 (13_Supplement): 964.
Published: 01 July 2021
...Jim A. Rotolo; Erin Gallagher; Lila Ghamsari; Siok Leong; Ricardo Ramirez; Mark Koester; Gene Merutka; Barry J. Kappel β-catenin is an oncogenic transcription factor that has an essential role in cell development and biology. Increased β-catenin expression or activity has been implicated in many...
Journal Articles
Cancer Res (2021) 81 (13_Supplement): 2857.
Published: 01 July 2021
... potential to drive metastasis but have nothing to increase cell proliferation. Furthermore, Wnt/β-catenin cascades were responsible for tumor mestasis among wild-type and amidotransferase-mutated type groups. The accumulation and nuclear location of β-catenin definitely depend on high ASNS expression even...
Journal Articles
Cancer Res (2021) 81 (13_Supplement): 1110.
Published: 01 July 2021
...-like properties, allowing these cells to survive and acquire resistance. Activation of β-catenin and downstream signaling components is one of the major pathways enabling this adaptive persistence. Our goal is to identify and validate β-catenin inhibitors that have the potential to improve the depth...
Journal Articles
Cancer Res (2021) 81 (13_Supplement): 1213.
Published: 01 July 2021
...) counterparts. Moreover, PDE10A inhibition decreased Wnt-induced β-catenin nuclear translocation as well as decreased EGF-mediated activation of RAS/MAPK and AKT pathways in ovarian cancer cells. RNA sequencing of SKOV3 PDE10A KO clones revealed that pathways associated with cancer, Wnt and TGF-β signaling were...
Journal Articles
Cancer Res (2021) 81 (13_Supplement): 1437.
Published: 01 July 2021
...Mizuki Kimura; Yusaku Hori; Megumi Kuronishi; Takayuki Kimura; Ryoga Ishida; Kenji Ichikawa; Yoichi Ozawa; Yu Kato Background: Aberrant activation of Wnt/β-catenin signaling plays an important role in both carcinogenesis and modulation of the tumor microenvironment. E7386, an investigational anti...
Journal Articles
Cancer Res (2021) 81 (12): 3229–3240.
Published: 15 June 2021
... with their EPHB2-Low counterparts. Mechanistically, EPHB2 regulated cancer stemness and drug resistance by driving the SRC/AKT/GSK3β/β-catenin signaling cascade, and EPHB2 expression was regulated by TCF1 via promoter activation, forming a positive Wnt/β-catenin feedback loop. Intravenous administration of rAAV-8...
Includes: Supplementary data
Journal Articles
Cancer Res (2021) 81 (8): 2029–2043.
Published: 15 April 2021
... exist for NRAS-mutant melanoma, motivating the search for additional therapeutic targets and vulnerable pathways. Here we identify a regulator of Wnt/β-catenin signaling, PLEKHA4, as a factor required for melanoma proliferation and survival. PLEKHA4 knockdown in vitro decreased Dishevelled...
Includes: Supplementary data
Journal Articles
Cancer Res (2021) 81 (8): 2157–2170.
Published: 15 April 2021
... tumors displayed activation of the Wnt/β-catenin signaling pathway. Chemical and genetic ALK inhibition suppressed Wnt/β-catenin signaling and tumor growth in vitro in NEPC and neuroblastoma cells. ALK inhibition cooperated with Wnt inhibition to suppress NEPC and neuroblastoma proliferation...
Includes: Supplementary data
Journal Articles
Series: Author Choice
Cancer Res (2021) 81 (8): 2116–2127.
Published: 15 April 2021
... the CSC population. Interfering with YAP activity delayed basal-like cancer formation, prevented luminal to basal transdifferentiation, and reduced CSC. YAP knockout mammary glands revealed a decrease in β-catenin target genes, suggesting that YAP is required for nuclear β-catenin activity...
Includes: Supplementary data
Journal Articles
Series: Author Choice
Cancer Res (2021) 81 (4): 1052–1062.
Published: 15 February 2021
...; Akira Yokoi; Masayuki Matsukura; Takenao Odagami; Masao Iwata; Akihiko Tsuruoka; Toshimitsu Uenaka; Junji Matsui; Tomohiro Matsushima; Kenichi Nomoto; Hiroyuki Kouji; Takashi Owa; Yasuhiro Funahashi; Yoichi Ozawa The Wnt/β-catenin signaling pathway plays crucial roles in embryonic development...
Includes: Supplementary data
Journal Articles
Cancer Res (2021) 81 (2): 464–475.
Published: 15 January 2021
...Nathan Harmston; Jun Yi Stanley Lim; Oriol Arqués; Héctor G. Palmer; Enrico Petretto; David M. Virshup; Babita Madan Aberrant Wnt signaling drives a number of cancers through regulation of diverse downstream pathways. Wnt/β-catenin signaling achieves this in part by increasing the expression...
Includes: Supplementary data
Images
Transcriptome profiling of canonical Wnt/<span class="search-highlight">β</span>-<span class="search-highlight">catenin</span> signaling in prostate ca...
Published: 15 April 2022
Figure 1. Transcriptome profiling of canonical Wnt/β-catenin signaling in prostate cancer cells. A, Differentially expressed genes between VCaP plus RNF43 knockdown with (n = 2) or without (n = 2) WNT3a stimulation (P < 0.05). B, Differentially expressed genes between VCaP with control siRNA (n = 2) and APC siRNA (n = 2; P < 0.05). C, Overlap of differentially expressed genes from the two treatments. D, Enriched pathways based on shared genes. E, Enriched pathways for genes regulated only by APC. Enrichment was by Metacore Pathway Enrichment Analysis, P < 0.01. Blue stripes, enrichment for the common 124 genes; orange solid bars, enrichment for genes uniquely regulated with RNF43i/WNT3a; blue solid bars, enrichment for genes uniquely regulated upon APC knockdown. Figure 1. Transcriptome profiling of canonical Wnt/β-catenin signaling in prostate cancer cells. A, Differentially expressed genes between VCaP plus RNF43 knockdown with (n = 2) or without (n = 2) WNT3a stimulation (P < 0.05). B, Differentially expressed genes between VCaP with control siRNA (n = 2) and APC siRNA (n = 2; P < 0.05). C, Overlap of differentially expressed genes from the two treatments. D, Enriched pathways based on shared genes. E, Enriched pathways for genes regulated only by APC. Enrichment was by Metacore Pathway Enrichment Analysis, P < 0.01. Blue stripes, enrichment for the common 124 genes; orange solid bars, enrichment for genes uniquely regulated with RNF43i/WNT3a; blue solid bars, enrichment for genes uniquely regulated upon APC knockdown. More
Images
Wnt/<span class="search-highlight">β</span>-<span class="search-highlight">catenin</span> activity is correlated with tumor cell expression of WLS.  A,...
Published: 15 April 2022
Figure 4. Wnt/β-catenin activity is correlated with tumor cell expression of WLS. A, Expression correlation between potential Wnt drivers and WNT activity in TCGA (n = 448) dataset. B, Representative IHC of WLS in prostate. Top left, normal prostate glands with magnified focus area. Top right, PIN lesions (black dashed line circles a PIN focus; black arrows, luminal tumor cells; green arrows, basal cells; red circles and arrows, surrounding tumor foci and lack of basal cells). Bottom, WLS in primary prostate cancer, with heterogeneous WLS expression shown in lower right (red arrow, tumor area with positive WLS staining). C, Correlation between WLS mRNA and Wnt activity in FHCRC (n = 149), WCPCDT (n = 99), and SU2C (n = 89) datasets. D, Representative IHC of WLS in a TMA of mCRPC (n = 20) showing a range from negative to strong staining patterns. A and C, statistics: Pearson correlations with linear regression, correlation scores (r), and P values are shown. Significant, P < 0.05. Figure 4. Wnt/β-catenin activity is correlated with tumor cell expression of WLS. A, Expression correlation between potential Wnt drivers and WNT activity in TCGA (n = 448) dataset. B, Representative IHC of WLS in prostate. Top left, normal prostate glands with magnified focus area. Top right, PIN lesions (black dashed line circles a PIN focus; black arrows, luminal tumor cells; green arrows, basal cells; red circles and arrows, surrounding tumor foci and lack of basal cells). Bottom, WLS in primary prostate cancer, with heterogeneous WLS expression shown in lower right (red arrow, tumor area with positive WLS staining). C, Correlation between WLS mRNA and Wnt activity in FHCRC (n = 149), WCPCDT (n = 99), and SU2C (n = 89) datasets. D, Representative IHC of WLS in a TMA of mCRPC (n = 20) showing a range from negative to strong staining patterns. A and C, statistics: Pearson correlations with linear regression, correlation scores (r), and P values are shown. Significant, P < 0.05. More
Images
Downstream effectors of canonical Wnt/<span class="search-highlight">β</span>-<span class="search-highlight">catenin</span> signaling in prostate cance...
Published: 15 April 2022
Figure 5. Downstream effectors of canonical Wnt/β-catenin signaling in prostate cancer. A, Random Forest analysis intersecting genes most correlated with Wnt/β-catenin pathway activation in TCGA dataset and in VCaP cells with APC knockdown and RNF43i/WNT3a stimulation. B, qRT-PCR for downstrea... More
Images
WNT/<span class="search-highlight">β</span>-<span class="search-highlight">catenin</span> signaling increases ROR1 <em>in vivo</em> and primes ...
Published: 15 April 2022
Figure 7. WNT/β-catenin signaling increases ROR1 in vivo and primes for noncanonical Wnt signaling. A–C , VCaP cells were treated with control or APC siRNA for 3 days, followed by stimulation with WNT5a for 6 hours and immunoblotting or qRT-PCR. A and B, p-Smad and p-CAMKII responses to WNT5a with increased ROR1 (representative of at least three replicates). C, qRT-PCR confirming APC depletion and showing that WNT5a is not increasing canonical Wnt/β-catenin target genes. D, Representative images of hematoxylin and eosin (H&E) and WLS IHC from multiple metastatic sites in ENZ-resistant rapid autopsy case. E, Representative image of WLS IHC from PDX BIDPC5 (BID5) generated from the case in D . F, Growth curves of PDX treated with vehicle (black; n = 3), ENZ (green; n = 3), or ETC-159 (red; n = 9). Statistics: Mann–Whitney test compared the difference between the ETC-159 and control arms. G, WNT/β-catenin effectors in response to PORCN inhibition compared with untreated controls from tumors collected at the treatment endpoints. Figure 7. WNT/β-catenin signaling increases ROR1 in vivo and primes for noncanonical Wnt signaling. A–C, VCaP cells were treated with control or APC siRNA for 3 days, followed by stimulation with WNT5a for 6 hours and immunoblotting or qRT-PCR. A and B, p-Smad and p-CAMKII responses to WNT5a with increased ROR1 (representative of at least three replicates). C, qRT-PCR confirming APC depletion and showing that WNT5a is not increasing canonical Wnt/β-catenin target genes. D, Representative images of hematoxylin and eosin (H&E) and WLS IHC from multiple metastatic sites in ENZ-resistant rapid autopsy case. E, Representative image of WLS IHC from PDX BIDPC5 (BID5) generated from the case in D. F, Growth curves of PDX treated with vehicle (black; n = 3), ENZ (green; n = 3), or ETC-159 (red; n = 9). Statistics: Mann–Whitney test compared the difference between the ETC-159 and control arms. G, WNT/β-catenin effectors in response to PORCN inhibition compared with untreated controls from tumors collected at the treatment endpoints. More
Journal Articles
Cancer Res (2021) 81 (1): 38–49.
Published: 04 January 2021
... that stabilize β-catenin and cause intestinal tumors in mice and humans. However, the mechanisms involved in genetically predisposed penetrance are not well understood. Here, we analyzed tumor multiplicity and gene expression in tumor-prone ApcMin/+ mice on highly variant C57BL/6J (B6...
Includes: Supplementary data