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Characterization of Collapsin Response Mediator Protein 2 in Colorectal Cancer Progression in Subjects with Diabetic Comorbidity
Background: Common demographic risk factors are identified in colorectal cancer (CRC) and type 2 diabetes mellitus (DM), nevertheless, the molecular link and mechanism for CRC-DM comorbidity remain elusive. Dysregulated glycogen synthase kinase-3 beta under metabolic imbalance is suggested to accele...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869905/ https://www.ncbi.nlm.nih.gov/pubmed/35203376 http://dx.doi.org/10.3390/cells11040727 |
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author | Chang, Yih-Hsin Yang, Hui-Ju Chen, Huan-Wen Hsiao, Chiao-Wan Hsieh, Yi-Chen Chan, Yu-Wei Chang, Shu-Wen Hwang, Wei-Lun Chen, Wei-Shone Cheng, Hou-Hsuan Chou, Teh-Ying Chang, Fu-Pang Ho, Hsiang-Ling Chu, Fang-Yeh Lo, Yu-Li Chen, Chun-Jung Tsai, Hui-Fang Shiau, Ming-Yuh |
author_facet | Chang, Yih-Hsin Yang, Hui-Ju Chen, Huan-Wen Hsiao, Chiao-Wan Hsieh, Yi-Chen Chan, Yu-Wei Chang, Shu-Wen Hwang, Wei-Lun Chen, Wei-Shone Cheng, Hou-Hsuan Chou, Teh-Ying Chang, Fu-Pang Ho, Hsiang-Ling Chu, Fang-Yeh Lo, Yu-Li Chen, Chun-Jung Tsai, Hui-Fang Shiau, Ming-Yuh |
author_sort | Chang, Yih-Hsin |
collection | PubMed |
description | Background: Common demographic risk factors are identified in colorectal cancer (CRC) and type 2 diabetes mellitus (DM), nevertheless, the molecular link and mechanism for CRC-DM comorbidity remain elusive. Dysregulated glycogen synthase kinase-3 beta under metabolic imbalance is suggested to accelerate CRC pathogenesis/progression via regulating collpasin response mediator protein-2 (CRMP2). Accordingly, roles of CRMP2 in CRC and CRC-DM patients were investigated for elucidating the molecular convergence of CRC and DM. Methods: CRMP2 profile in tumor tissues from CRC and CRC-DM patients was investigated to explore the link between CRC and DM etiology. Meanwhile, molecular mechanism of glucose to regulate CRMP2 profile and CRC characteristics was examined in vitro and in vivo. Results: CRMP2 was significantly lower in tumor lesions and associated with advanced tumor stage in CRC-DM patients. Physiological hyperglycemia suppressed CRMP2 expression/activity and augmented malignant characteristics of CRC cells. Hyperglycemia promotes actin de-polymerization, cytoskeleton flexibility and cell proliferation/metastasis by downregulating CRMP2 profile and thus contributes to CRC disease progression. Conclusions: This study uncovers molecular evidence to substantiate and elucidate the link between CRC and T2DM, as well as characterizing the roles of CRMP2 in CRC-DM. Accordingly, altered metabolic adaptations are promising targets for anti-diabetic and cancer strategies. |
format | Online Article Text |
id | pubmed-8869905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88699052022-02-25 Characterization of Collapsin Response Mediator Protein 2 in Colorectal Cancer Progression in Subjects with Diabetic Comorbidity Chang, Yih-Hsin Yang, Hui-Ju Chen, Huan-Wen Hsiao, Chiao-Wan Hsieh, Yi-Chen Chan, Yu-Wei Chang, Shu-Wen Hwang, Wei-Lun Chen, Wei-Shone Cheng, Hou-Hsuan Chou, Teh-Ying Chang, Fu-Pang Ho, Hsiang-Ling Chu, Fang-Yeh Lo, Yu-Li Chen, Chun-Jung Tsai, Hui-Fang Shiau, Ming-Yuh Cells Article Background: Common demographic risk factors are identified in colorectal cancer (CRC) and type 2 diabetes mellitus (DM), nevertheless, the molecular link and mechanism for CRC-DM comorbidity remain elusive. Dysregulated glycogen synthase kinase-3 beta under metabolic imbalance is suggested to accelerate CRC pathogenesis/progression via regulating collpasin response mediator protein-2 (CRMP2). Accordingly, roles of CRMP2 in CRC and CRC-DM patients were investigated for elucidating the molecular convergence of CRC and DM. Methods: CRMP2 profile in tumor tissues from CRC and CRC-DM patients was investigated to explore the link between CRC and DM etiology. Meanwhile, molecular mechanism of glucose to regulate CRMP2 profile and CRC characteristics was examined in vitro and in vivo. Results: CRMP2 was significantly lower in tumor lesions and associated with advanced tumor stage in CRC-DM patients. Physiological hyperglycemia suppressed CRMP2 expression/activity and augmented malignant characteristics of CRC cells. Hyperglycemia promotes actin de-polymerization, cytoskeleton flexibility and cell proliferation/metastasis by downregulating CRMP2 profile and thus contributes to CRC disease progression. Conclusions: This study uncovers molecular evidence to substantiate and elucidate the link between CRC and T2DM, as well as characterizing the roles of CRMP2 in CRC-DM. Accordingly, altered metabolic adaptations are promising targets for anti-diabetic and cancer strategies. MDPI 2022-02-18 /pmc/articles/PMC8869905/ /pubmed/35203376 http://dx.doi.org/10.3390/cells11040727 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chang, Yih-Hsin Yang, Hui-Ju Chen, Huan-Wen Hsiao, Chiao-Wan Hsieh, Yi-Chen Chan, Yu-Wei Chang, Shu-Wen Hwang, Wei-Lun Chen, Wei-Shone Cheng, Hou-Hsuan Chou, Teh-Ying Chang, Fu-Pang Ho, Hsiang-Ling Chu, Fang-Yeh Lo, Yu-Li Chen, Chun-Jung Tsai, Hui-Fang Shiau, Ming-Yuh Characterization of Collapsin Response Mediator Protein 2 in Colorectal Cancer Progression in Subjects with Diabetic Comorbidity |
title | Characterization of Collapsin Response Mediator Protein 2 in Colorectal Cancer Progression in Subjects with Diabetic Comorbidity |
title_full | Characterization of Collapsin Response Mediator Protein 2 in Colorectal Cancer Progression in Subjects with Diabetic Comorbidity |
title_fullStr | Characterization of Collapsin Response Mediator Protein 2 in Colorectal Cancer Progression in Subjects with Diabetic Comorbidity |
title_full_unstemmed | Characterization of Collapsin Response Mediator Protein 2 in Colorectal Cancer Progression in Subjects with Diabetic Comorbidity |
title_short | Characterization of Collapsin Response Mediator Protein 2 in Colorectal Cancer Progression in Subjects with Diabetic Comorbidity |
title_sort | characterization of collapsin response mediator protein 2 in colorectal cancer progression in subjects with diabetic comorbidity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869905/ https://www.ncbi.nlm.nih.gov/pubmed/35203376 http://dx.doi.org/10.3390/cells11040727 |
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