Retinoid signaling in pancreatic cancer, injury and regeneration.
<h4>Background</h4>Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC). These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clini...
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2011
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oai:doaj.org-article:b3fd6bce0bff466abcff9a2bfaea146b2021-11-18T07:31:18ZRetinoid signaling in pancreatic cancer, injury and regeneration.1932-620310.1371/journal.pone.0029075https://doaj.org/article/b3fd6bce0bff466abcff9a2bfaea146b2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22220202/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC). These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC.<h4>Methodology/principal findings</h4>We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1), a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A). However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies.<h4>Conclusions/significance</h4>In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1.Emily K ColvinJohana M SusantoJames G KenchVivienna N OngAmanda MawsonMark PineseDavid K ChangIlse RoomanSandra A O'TooleDavendra SegaraElizabeth A MusgroveRobert L SutherlandMinoti V ApteChristopher J ScarlettAndrew V BiankinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 12, p e29075 (2011) |
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| topic |
Medicine R Science Q |
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Medicine R Science Q Emily K Colvin Johana M Susanto James G Kench Vivienna N Ong Amanda Mawson Mark Pinese David K Chang Ilse Rooman Sandra A O'Toole Davendra Segara Elizabeth A Musgrove Robert L Sutherland Minoti V Apte Christopher J Scarlett Andrew V Biankin Retinoid signaling in pancreatic cancer, injury and regeneration. |
| description |
<h4>Background</h4>Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC). These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC.<h4>Methodology/principal findings</h4>We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1), a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A). However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies.<h4>Conclusions/significance</h4>In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1. |
| format |
article |
| author |
Emily K Colvin Johana M Susanto James G Kench Vivienna N Ong Amanda Mawson Mark Pinese David K Chang Ilse Rooman Sandra A O'Toole Davendra Segara Elizabeth A Musgrove Robert L Sutherland Minoti V Apte Christopher J Scarlett Andrew V Biankin |
| author_facet |
Emily K Colvin Johana M Susanto James G Kench Vivienna N Ong Amanda Mawson Mark Pinese David K Chang Ilse Rooman Sandra A O'Toole Davendra Segara Elizabeth A Musgrove Robert L Sutherland Minoti V Apte Christopher J Scarlett Andrew V Biankin |
| author_sort |
Emily K Colvin |
| title |
Retinoid signaling in pancreatic cancer, injury and regeneration. |
| title_short |
Retinoid signaling in pancreatic cancer, injury and regeneration. |
| title_full |
Retinoid signaling in pancreatic cancer, injury and regeneration. |
| title_fullStr |
Retinoid signaling in pancreatic cancer, injury and regeneration. |
| title_full_unstemmed |
Retinoid signaling in pancreatic cancer, injury and regeneration. |
| title_sort |
retinoid signaling in pancreatic cancer, injury and regeneration. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/b3fd6bce0bff466abcff9a2bfaea146b |
| work_keys_str_mv |
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