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Jose Ortiz and Teresa Ku on trefoil factor 2 expression by pancreatic acinar cells, Adrian Vella ...
Welcome to the September 2024 episode of DiabetesBio—the American Diabetes Association’s podcast for its flagship research publication, Diabetes (https://diabetesjournals.org/diabetes) . In this episode of DiabetesBio, Drs. Kirk Habegger, Darleen Sandoval, and Kevin Williams discuss the latest and greatest content in the September 2024 issue of Diabetes and interview a Pathway to Stop Diabetes award winner.
4:20: Darleen and Kirk are joined by Jose A. Ortiz (https://www.linkedin.com/in/joseortiz8) and Hsun Teresa Ku (https://www.cityofhope.org/hsun-ku) , first and last authors of “Trefoil Factor 2 Expressed by the Murine Pancreatic Acinar Cells Is Required for the Development of Islets and for β-Cell Function During Aging.” This article is an editor-selected feature article and is ...
published: 04 Sep 2024
-
Gene Music Using Protein Sequence of TFF2 "TREFOIL FACTOR 2"
Shop TFF2 - https://www.redbubble.com/people/genemusic/works/43968259-tff2?asc=u
Subscribe - https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences)
Gene Music using Protein Sequence of TFF2 'TREFOIL FACTOR 2'
published: 25 Nov 2015
-
TFF1 and TFF3 predict response to CDK4/6 inhibitors in breast cancer patients
Khandan Keyomarsi, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX, comments on Trefoil Factor 1 and 3 (TFF1 and TFF3) as potential biomarkers of response to CDK4/6 inhibitors in patients with ER-positive, HER2-negative breast cancer. An analysis of breast cancer cell lines revealed the two secretory proteins to be promising biomarkers, enabling enhanced selection of patients who will benefit from CDK4/6 inhibitors. This interview took place at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, FL.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
published: 19 Apr 2023
-
Alarming controversies in IL-33 biology by Dr. De’Broski Herbert
GLOBAL IMMUNOTALK 11-03-21
published: 03 Nov 2021
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An introduction to the Trefoil system by Dr. Kenji Higuchi
In the above video you can preview the exclusive presentation by Dr. Kenji Higuchi on the Trefoil system. The full 20-minute presentation covers you can find here http://info.nobelbiocare.com/int/en/trefoil-video-lecture-higuchi
published: 30 Nov 2017
-
Physiology Shorts: Effectors of gastric epithelial repair
In this Physiology Shorts video, Kristen Engevik (Baylor College of Medicine, US) and Chip Montrose (University of Cincinnati, US) discuss their latest research into the effectors that drive gastric epithelial repair .
Read more about this research in The Journal of Physiology:
Trefoil factor 2 activation of CXCR4 requires calciummobilization to drive epithelial repair in gastric organoids
Kristen A. Engevik, Hikaru Hanyu, Andrea L. Matthis, Tongli Zhang, Mark R. Frey, Yusuke Oshima, Eitaro Aihara & Marshall H. Montrose.
597(10), pp. 2673–2690.
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP277259?af=R
Transcript:
Hi, my name is Chip Montrose, I’m from the University of Cincinnati and my partner is: I’m Kristen Engevik, formerly from the University of Cincinnati and now I’m...
published: 02 Oct 2019
-
Loss of TFF2 in Pancreatic Duct Glands results in the formation of IPMN, Junpei Yamaguchi, MD, PhD
APA/Hirshberg Symposium: Celebrating 10 Years of the Hirshberg Seed Grant
The 2013 Winner of the Hirshberg Award for Best Basic Science Abstract in Pancreatic Cancer
Presented to: Junpei Yamaguchi, MD, PhD
Massachusetts General Hospital and Harvard Medical School
Loss of TFF2 in Pancreatic Duct Glands (PDG) results in the formation of IPMN suggesting TFF2 may function as a tumor suppressor.
Background: PDG are a novel epithelial progenitor compartment important for regeneration of the ductal epithelium. Our early correlative studies suggest that dysregulation of this compartment may result in formation of IPMN. This compartment uniquely expresses trefoil family factor 2 (TFF2). PDG functionally and molecularly resemble gastric glands. In the stomach TFF2 has been reported to be th...
published: 13 Nov 2013
-
Gene Music using Protein Sequence of TFF1 "TREFOIL FACTOR 1"
Shop TFF1 - https://www.redbubble.com/people/genemusic/works/43968147-tff1?asc=u
Subscribe - https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences)
Gene Music using Protein Sequence of TFF1 'TREFOIL FACTOR 1'
published: 03 Sep 2016
-
the new al-nassr jersey is 👌🔥✨ #alnassr #adidas #football
Find out more at http://www.adidas.com
Follow us:
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TikTok - https://www.tiktok.com/@adidas
published: 10 Aug 2024
-
Activation of β-catenin signalling by TFF1 loss
Promotes cell proliferation and gastric tumorigenesis.
Read the full paper: http://gut.bmj.com/content/early/2014/08/08/gutjnl-2014-307191.full
Abstract
Objective
In this study, we investigated the role of Trefoil factor 1 in regulating cell proliferation and tumour development through β-catenin signalling using in vivo and in vitro models of gastric tumorigenesis.
Design
Tff1-knockout mice, immunohistochemistry, luciferase reporter, qRT-PCR, immunoblot, and phosphatase assays were used to examine the role of TFF1 on β-catenin signalling pathway.
Results
Nuclear localisation of β-catenin with transcriptional upregulation of its target genes, c-Myc and Ccnd1, was detected in hyperplastic tissue at an early age of 4–6 weeks and maintained during all stages of gastric tumorigenesis in...
published: 13 Jul 2015
1:02:27
Jose Ortiz and Teresa Ku on trefoil factor 2 expression by pancreatic acinar cells, Adrian Vella ...
Welcome to the September 2024 episode of DiabetesBio—the American Diabetes Association’s podcast for its flagship research publication, Diabetes (https://diabe...
Welcome to the September 2024 episode of DiabetesBio—the American Diabetes Association’s podcast for its flagship research publication, Diabetes (https://diabetesjournals.org/diabetes) . In this episode of DiabetesBio, Drs. Kirk Habegger, Darleen Sandoval, and Kevin Williams discuss the latest and greatest content in the September 2024 issue of Diabetes and interview a Pathway to Stop Diabetes award winner.
4:20: Darleen and Kirk are joined by Jose A. Ortiz (https://www.linkedin.com/in/joseortiz8) and Hsun Teresa Ku (https://www.cityofhope.org/hsun-ku) , first and last authors of “Trefoil Factor 2 Expressed by the Murine Pancreatic Acinar Cells Is Required for the Development of Islets and for β-Cell Function During Aging.” This article is an editor-selected feature article and is freely accessible at https://doi.org/10.2337/db23-0490.
25:07: Kirk and Darleen talk to Adrian Vella (https://www.mayo.edu/research/faculty/vella-adrian-m-d/bio-00027295) , last author of “The Longitudinal Effect of Diabetes-Associated Variation in TCF7L2 on Islet Function in Humans.” This article is also an editor-selected feature article and is freely accessible at https://doi.org/10.2337/db24-0192.
50:21: In this month’s Sweet Talk segment, Kevin chats with Matthew J. Webber (https://cbe.nd.edu/faculty/matthew-webber/) , a 2019 Pathway to Stop Diabetes (https://diabetes.org/research/pathway) Accelerator Award winner, about his research on materials that can sense and respond to changing glucose.
To learn more about Diabetes and DiabetesBio, please visit diabetesjournals.org/diabetes (https://diabetesjournals.org/diabetes) . Thank you for listening, and don’t forget to smash that “follow” button!
https://wn.com/Jose_Ortiz_And_Teresa_Ku_On_Trefoil_Factor_2_Expression_By_Pancreatic_Acinar_Cells,_Adrian_Vella_...
Welcome to the September 2024 episode of DiabetesBio—the American Diabetes Association’s podcast for its flagship research publication, Diabetes (https://diabetesjournals.org/diabetes) . In this episode of DiabetesBio, Drs. Kirk Habegger, Darleen Sandoval, and Kevin Williams discuss the latest and greatest content in the September 2024 issue of Diabetes and interview a Pathway to Stop Diabetes award winner.
4:20: Darleen and Kirk are joined by Jose A. Ortiz (https://www.linkedin.com/in/joseortiz8) and Hsun Teresa Ku (https://www.cityofhope.org/hsun-ku) , first and last authors of “Trefoil Factor 2 Expressed by the Murine Pancreatic Acinar Cells Is Required for the Development of Islets and for β-Cell Function During Aging.” This article is an editor-selected feature article and is freely accessible at https://doi.org/10.2337/db23-0490.
25:07: Kirk and Darleen talk to Adrian Vella (https://www.mayo.edu/research/faculty/vella-adrian-m-d/bio-00027295) , last author of “The Longitudinal Effect of Diabetes-Associated Variation in TCF7L2 on Islet Function in Humans.” This article is also an editor-selected feature article and is freely accessible at https://doi.org/10.2337/db24-0192.
50:21: In this month’s Sweet Talk segment, Kevin chats with Matthew J. Webber (https://cbe.nd.edu/faculty/matthew-webber/) , a 2019 Pathway to Stop Diabetes (https://diabetes.org/research/pathway) Accelerator Award winner, about his research on materials that can sense and respond to changing glucose.
To learn more about Diabetes and DiabetesBio, please visit diabetesjournals.org/diabetes (https://diabetesjournals.org/diabetes) . Thank you for listening, and don’t forget to smash that “follow” button!
- published: 04 Sep 2024
- views: 76
0:35
Gene Music Using Protein Sequence of TFF2 "TREFOIL FACTOR 2"
Shop TFF2 - https://www.redbubble.com/people/genemusic/works/43968259-tff2?asc=u
Subscribe - https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene M...
Shop TFF2 - https://www.redbubble.com/people/genemusic/works/43968259-tff2?asc=u
Subscribe - https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences)
Gene Music using Protein Sequence of TFF2 'TREFOIL FACTOR 2'
https://wn.com/Gene_Music_Using_Protein_Sequence_Of_Tff2_Trefoil_Factor_2
Shop TFF2 - https://www.redbubble.com/people/genemusic/works/43968259-tff2?asc=u
Subscribe - https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences)
Gene Music using Protein Sequence of TFF2 'TREFOIL FACTOR 2'
- published: 25 Nov 2015
- views: 24
3:14
TFF1 and TFF3 predict response to CDK4/6 inhibitors in breast cancer patients
Khandan Keyomarsi, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX, comments on Trefoil Factor 1 and 3 (TFF1 and TFF3) as potential biomarke...
Khandan Keyomarsi, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX, comments on Trefoil Factor 1 and 3 (TFF1 and TFF3) as potential biomarkers of response to CDK4/6 inhibitors in patients with ER-positive, HER2-negative breast cancer. An analysis of breast cancer cell lines revealed the two secretory proteins to be promising biomarkers, enabling enhanced selection of patients who will benefit from CDK4/6 inhibitors. This interview took place at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, FL.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
https://wn.com/Tff1_And_Tff3_Predict_Response_To_Cdk4_6_Inhibitors_In_Breast_Cancer_Patients
Khandan Keyomarsi, PhD, The University of Texas MD Anderson Cancer Center, Houston, TX, comments on Trefoil Factor 1 and 3 (TFF1 and TFF3) as potential biomarkers of response to CDK4/6 inhibitors in patients with ER-positive, HER2-negative breast cancer. An analysis of breast cancer cell lines revealed the two secretory proteins to be promising biomarkers, enabling enhanced selection of patients who will benefit from CDK4/6 inhibitors. This interview took place at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando, FL.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
- published: 19 Apr 2023
- views: 165
1:04
An introduction to the Trefoil system by Dr. Kenji Higuchi
In the above video you can preview the exclusive presentation by Dr. Kenji Higuchi on the Trefoil system. The full 20-minute presentation covers you can find he...
In the above video you can preview the exclusive presentation by Dr. Kenji Higuchi on the Trefoil system. The full 20-minute presentation covers you can find here http://info.nobelbiocare.com/int/en/trefoil-video-lecture-higuchi
https://wn.com/An_Introduction_To_The_Trefoil_System_By_Dr._Kenji_Higuchi
In the above video you can preview the exclusive presentation by Dr. Kenji Higuchi on the Trefoil system. The full 20-minute presentation covers you can find here http://info.nobelbiocare.com/int/en/trefoil-video-lecture-higuchi
- published: 30 Nov 2017
- views: 8216
1:51
Physiology Shorts: Effectors of gastric epithelial repair
In this Physiology Shorts video, Kristen Engevik (Baylor College of Medicine, US) and Chip Montrose (University of Cincinnati, US) discuss their latest research...
In this Physiology Shorts video, Kristen Engevik (Baylor College of Medicine, US) and Chip Montrose (University of Cincinnati, US) discuss their latest research into the effectors that drive gastric epithelial repair .
Read more about this research in The Journal of Physiology:
Trefoil factor 2 activation of CXCR4 requires calciummobilization to drive epithelial repair in gastric organoids
Kristen A. Engevik, Hikaru Hanyu, Andrea L. Matthis, Tongli Zhang, Mark R. Frey, Yusuke Oshima, Eitaro Aihara & Marshall H. Montrose.
597(10), pp. 2673–2690.
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP277259?af=R
Transcript:
Hi, my name is Chip Montrose, I’m from the University of Cincinnati and my partner is: I’m Kristen Engevik, formerly from the University of Cincinnati and now I’m doing my postdoc down at Baylor College of Medicine.
This is a really nice opportunity for Kristen and I to get back together because Dr. Engevik has left the laboratory so this is our chance to get back together in the beautiful setting of Colorado where we’re having a conference together. And so we hope you enjoy the backdrop, it’s a little bit better than a laboratory setting.
So our study has been focusing on the signaling mechanism within the epithelial cells during repair in the stomach. And so, to do this we utilized the in vitro mouse gastric organoids in order for us to study the innate response within the epithelial cells. And so using this, we wanted to look into the calcium signaling that is essential for proper repair to occur and look into potential upstream and downstream effectors of this. So we found that trefoil factor 2 acts via CXCR4 and potentially EGFR to initiate calcium signaling within the cells and that downstream of calcium signaling we also find that the sodium hydrogen exchanger 2 is also involved and that all these components are essential for proper repair within these epithelial cells to occur.
And so we hope that this will help us learn more about the pathways that can be improved during pathological processes when repair is compromised. And the organoid system has really been a very valuable tool to dissect this better than we can in vivo, it really has been a benefit for us. And we hope for others as they go and feed off these studies into further ones.
So thank you very much for paying attention to our article in the Journal of Physiology. You can find it in volume 597, in issue 10. And we hope you enjoy it. Thank you.
https://wn.com/Physiology_Shorts_Effectors_Of_Gastric_Epithelial_Repair
In this Physiology Shorts video, Kristen Engevik (Baylor College of Medicine, US) and Chip Montrose (University of Cincinnati, US) discuss their latest research into the effectors that drive gastric epithelial repair .
Read more about this research in The Journal of Physiology:
Trefoil factor 2 activation of CXCR4 requires calciummobilization to drive epithelial repair in gastric organoids
Kristen A. Engevik, Hikaru Hanyu, Andrea L. Matthis, Tongli Zhang, Mark R. Frey, Yusuke Oshima, Eitaro Aihara & Marshall H. Montrose.
597(10), pp. 2673–2690.
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP277259?af=R
Transcript:
Hi, my name is Chip Montrose, I’m from the University of Cincinnati and my partner is: I’m Kristen Engevik, formerly from the University of Cincinnati and now I’m doing my postdoc down at Baylor College of Medicine.
This is a really nice opportunity for Kristen and I to get back together because Dr. Engevik has left the laboratory so this is our chance to get back together in the beautiful setting of Colorado where we’re having a conference together. And so we hope you enjoy the backdrop, it’s a little bit better than a laboratory setting.
So our study has been focusing on the signaling mechanism within the epithelial cells during repair in the stomach. And so, to do this we utilized the in vitro mouse gastric organoids in order for us to study the innate response within the epithelial cells. And so using this, we wanted to look into the calcium signaling that is essential for proper repair to occur and look into potential upstream and downstream effectors of this. So we found that trefoil factor 2 acts via CXCR4 and potentially EGFR to initiate calcium signaling within the cells and that downstream of calcium signaling we also find that the sodium hydrogen exchanger 2 is also involved and that all these components are essential for proper repair within these epithelial cells to occur.
And so we hope that this will help us learn more about the pathways that can be improved during pathological processes when repair is compromised. And the organoid system has really been a very valuable tool to dissect this better than we can in vivo, it really has been a benefit for us. And we hope for others as they go and feed off these studies into further ones.
So thank you very much for paying attention to our article in the Journal of Physiology. You can find it in volume 597, in issue 10. And we hope you enjoy it. Thank you.
- published: 02 Oct 2019
- views: 174
9:14
Loss of TFF2 in Pancreatic Duct Glands results in the formation of IPMN, Junpei Yamaguchi, MD, PhD
APA/Hirshberg Symposium: Celebrating 10 Years of the Hirshberg Seed Grant
The 2013 Winner of the Hirshberg Award for Best Basic Science Abstract in Pancreatic ...
APA/Hirshberg Symposium: Celebrating 10 Years of the Hirshberg Seed Grant
The 2013 Winner of the Hirshberg Award for Best Basic Science Abstract in Pancreatic Cancer
Presented to: Junpei Yamaguchi, MD, PhD
Massachusetts General Hospital and Harvard Medical School
Loss of TFF2 in Pancreatic Duct Glands (PDG) results in the formation of IPMN suggesting TFF2 may function as a tumor suppressor.
Background: PDG are a novel epithelial progenitor compartment important for regeneration of the ductal epithelium. Our early correlative studies suggest that dysregulation of this compartment may result in formation of IPMN. This compartment uniquely expresses trefoil family factor 2 (TFF2). PDG functionally and molecularly resemble gastric glands. In the stomach TFF2 has been reported to be the tumor suppressor of gastric cancer, suggesting that TFF2 also act as the tumor suppressor to prevent the initiation of pancreatic mucinous neoplasms.
Abstract Conclusions: TFF2 act as the tumor suppressor in PDG. This effect may be mediated by its effect on SMAD 4.
https://wn.com/Loss_Of_Tff2_In_Pancreatic_Duct_Glands_Results_In_The_Formation_Of_Ipmn,_Junpei_Yamaguchi,_Md,_Phd
APA/Hirshberg Symposium: Celebrating 10 Years of the Hirshberg Seed Grant
The 2013 Winner of the Hirshberg Award for Best Basic Science Abstract in Pancreatic Cancer
Presented to: Junpei Yamaguchi, MD, PhD
Massachusetts General Hospital and Harvard Medical School
Loss of TFF2 in Pancreatic Duct Glands (PDG) results in the formation of IPMN suggesting TFF2 may function as a tumor suppressor.
Background: PDG are a novel epithelial progenitor compartment important for regeneration of the ductal epithelium. Our early correlative studies suggest that dysregulation of this compartment may result in formation of IPMN. This compartment uniquely expresses trefoil family factor 2 (TFF2). PDG functionally and molecularly resemble gastric glands. In the stomach TFF2 has been reported to be the tumor suppressor of gastric cancer, suggesting that TFF2 also act as the tumor suppressor to prevent the initiation of pancreatic mucinous neoplasms.
Abstract Conclusions: TFF2 act as the tumor suppressor in PDG. This effect may be mediated by its effect on SMAD 4.
- published: 13 Nov 2013
- views: 365
1:26
Gene Music using Protein Sequence of TFF1 "TREFOIL FACTOR 1"
Shop TFF1 - https://www.redbubble.com/people/genemusic/works/43968147-tff1?asc=u
Subscribe - https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene M...
Shop TFF1 - https://www.redbubble.com/people/genemusic/works/43968147-tff1?asc=u
Subscribe - https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences)
Gene Music using Protein Sequence of TFF1 'TREFOIL FACTOR 1'
https://wn.com/Gene_Music_Using_Protein_Sequence_Of_Tff1_Trefoil_Factor_1
Shop TFF1 - https://www.redbubble.com/people/genemusic/works/43968147-tff1?asc=u
Subscribe - https://www.youtube.com/c/GeneMusicStudio?sub_confirmation=1
Gene Music Studio - A channel to taste (visually & musically) gene information (particularly protein sequences)
Gene Music using Protein Sequence of TFF1 'TREFOIL FACTOR 1'
- published: 03 Sep 2016
- views: 46
0:18
the new al-nassr jersey is 👌🔥✨ #alnassr #adidas #football
Find out more at http://www.adidas.com
Follow us:
Instagram - http://www.instagram.com/adidas
Twitter - https://www.twitter.com/adidas
TikTok - https://www.ti...
Find out more at http://www.adidas.com
Follow us:
Instagram - http://www.instagram.com/adidas
Twitter - https://www.twitter.com/adidas
TikTok - https://www.tiktok.com/@adidas
https://wn.com/The_New_Al_Nassr_Jersey_Is_👌🔥✨_Alnassr_Adidas_Football
Find out more at http://www.adidas.com
Follow us:
Instagram - http://www.instagram.com/adidas
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TikTok - https://www.tiktok.com/@adidas
- published: 10 Aug 2024
- views: 363922
3:34
Activation of β-catenin signalling by TFF1 loss
Promotes cell proliferation and gastric tumorigenesis.
Read the full paper: http://gut.bmj.com/content/early/2014/08/08/gutjnl-2014-307191.full
Abstract
Obje...
Promotes cell proliferation and gastric tumorigenesis.
Read the full paper: http://gut.bmj.com/content/early/2014/08/08/gutjnl-2014-307191.full
Abstract
Objective
In this study, we investigated the role of Trefoil factor 1 in regulating cell proliferation and tumour development through β-catenin signalling using in vivo and in vitro models of gastric tumorigenesis.
Design
Tff1-knockout mice, immunohistochemistry, luciferase reporter, qRT-PCR, immunoblot, and phosphatase assays were used to examine the role of TFF1 on β-catenin signalling pathway.
Results
Nuclear localisation of β-catenin with transcriptional upregulation of its target genes, c-Myc and Ccnd1, was detected in hyperplastic tissue at an early age of 4–6 weeks and maintained during all stages of gastric tumorigenesis in the Tff1-KO mice. The reconstitution of TFF1 or TFF1 conditioned media significantly inhibited the β-catenin/T-cell factor transcription activity in MKN28 gastric cancer cells. In agreement with these results, we detected a reduction in the levels of nuclear β-catenin with downregulation of c-MYC and CCND1 mRNA. Analysis of signalling molecules upstream of β-catenin revealed a decrease in phosphorylated glycogen synthase kinase 3β and p-AKT protein levels following the reconstitution of TFF1 expression; this was consistent with the increase of p-β-catenin and decrease of p-β-catenin. This TFF1-induced reduction in phosphorylation of GSK3β, and AKT was dependent on protein phosphatase 2A activity. The treatment with okadaic acid or knockdown of PP2A abrogated these effects. Consistent with the mouse data, we observed loss of TFF1 and an increase in nuclear localisation of β-catenin in stages of human gastric tumorigenesis.
Conclusions
Our data indicate that loss of TFF1 promotes β-catenin activation and gastric tumorigenesis through regulation of PP2A, a major regulator of AKT-GSK3β signalling.
https://wn.com/Activation_Of_Β_Catenin_Signalling_By_Tff1_Loss
Promotes cell proliferation and gastric tumorigenesis.
Read the full paper: http://gut.bmj.com/content/early/2014/08/08/gutjnl-2014-307191.full
Abstract
Objective
In this study, we investigated the role of Trefoil factor 1 in regulating cell proliferation and tumour development through β-catenin signalling using in vivo and in vitro models of gastric tumorigenesis.
Design
Tff1-knockout mice, immunohistochemistry, luciferase reporter, qRT-PCR, immunoblot, and phosphatase assays were used to examine the role of TFF1 on β-catenin signalling pathway.
Results
Nuclear localisation of β-catenin with transcriptional upregulation of its target genes, c-Myc and Ccnd1, was detected in hyperplastic tissue at an early age of 4–6 weeks and maintained during all stages of gastric tumorigenesis in the Tff1-KO mice. The reconstitution of TFF1 or TFF1 conditioned media significantly inhibited the β-catenin/T-cell factor transcription activity in MKN28 gastric cancer cells. In agreement with these results, we detected a reduction in the levels of nuclear β-catenin with downregulation of c-MYC and CCND1 mRNA. Analysis of signalling molecules upstream of β-catenin revealed a decrease in phosphorylated glycogen synthase kinase 3β and p-AKT protein levels following the reconstitution of TFF1 expression; this was consistent with the increase of p-β-catenin and decrease of p-β-catenin. This TFF1-induced reduction in phosphorylation of GSK3β, and AKT was dependent on protein phosphatase 2A activity. The treatment with okadaic acid or knockdown of PP2A abrogated these effects. Consistent with the mouse data, we observed loss of TFF1 and an increase in nuclear localisation of β-catenin in stages of human gastric tumorigenesis.
Conclusions
Our data indicate that loss of TFF1 promotes β-catenin activation and gastric tumorigenesis through regulation of PP2A, a major regulator of AKT-GSK3β signalling.
- published: 13 Jul 2015
- views: 1353