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CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt

Abnormal glucose metabolism may contribute to cancer progression. As a member of the CRK (v‐crk sarcoma virus CT10 oncogene homologue) adapter protein family, CRKL (CRK‐like) associated with the development and progression of various tumours. However, the exact role and underlying mechanism of CRKL...

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Autores principales: Guo, Chunmei, Gao, Chao, Lv, Xinxin, Zhao, Dongting, Greenaway, Frederick T., Hao, Lihong, Tian, Yuxiang, Liu, Shuqing, Sun, Ming‐Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933966/
https://www.ncbi.nlm.nih.gov/pubmed/33523562
http://dx.doi.org/10.1111/jcmm.16303
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author Guo, Chunmei
Gao, Chao
Lv, Xinxin
Zhao, Dongting
Greenaway, Frederick T.
Hao, Lihong
Tian, Yuxiang
Liu, Shuqing
Sun, Ming‐Zhong
author_facet Guo, Chunmei
Gao, Chao
Lv, Xinxin
Zhao, Dongting
Greenaway, Frederick T.
Hao, Lihong
Tian, Yuxiang
Liu, Shuqing
Sun, Ming‐Zhong
author_sort Guo, Chunmei
collection PubMed
description Abnormal glucose metabolism may contribute to cancer progression. As a member of the CRK (v‐crk sarcoma virus CT10 oncogene homologue) adapter protein family, CRKL (CRK‐like) associated with the development and progression of various tumours. However, the exact role and underlying mechanism of CRKL on energy metabolism remain unknown. In this study, we investigated the effect of CRKL on glucose metabolism of hepatocarcinoma cells. CRKL and PI3K were found to be overexpressed in both hepatocarcinoma cells and tissues; meanwhile, CRKL up‐regulation was positively correlated with PI3K up‐regulation. Functional investigations revealed that CRKL overexpression promoted glucose uptake, lactate production and glycogen synthesis of hepatocarcinoma cells by up‐regulating glucose transporters 1 (GLUT1), hexokinase II (HKII) expression and down‐regulating glycogen synthase kinase 3β (GSK3β) expression. Mechanistically, CRKL promoted glucose metabolism of hepatocarcinoma cells via enhancing the CRKL‐PI3K/Akt‐GLUT1/HKII‐glucose uptake, CRKL‐PI3K/Akt‐HKII‐glucose‐lactate production and CRKL‐PI3K/Akt‐Gsk3β‐glycogen synthesis. We demonstrate CRKL facilitates HCC malignancy via enhancing glucose uptake, lactate production and glycogen synthesis through PI3K/Akt pathway. It provides interesting fundamental clues to CRKL‐related carcinogenesis through glucose metabolism and offers novel therapeutic strategies for hepatocarcinoma.
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spelling pubmed-79339662021-03-15 CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt Guo, Chunmei Gao, Chao Lv, Xinxin Zhao, Dongting Greenaway, Frederick T. Hao, Lihong Tian, Yuxiang Liu, Shuqing Sun, Ming‐Zhong J Cell Mol Med Original Articles Abnormal glucose metabolism may contribute to cancer progression. As a member of the CRK (v‐crk sarcoma virus CT10 oncogene homologue) adapter protein family, CRKL (CRK‐like) associated with the development and progression of various tumours. However, the exact role and underlying mechanism of CRKL on energy metabolism remain unknown. In this study, we investigated the effect of CRKL on glucose metabolism of hepatocarcinoma cells. CRKL and PI3K were found to be overexpressed in both hepatocarcinoma cells and tissues; meanwhile, CRKL up‐regulation was positively correlated with PI3K up‐regulation. Functional investigations revealed that CRKL overexpression promoted glucose uptake, lactate production and glycogen synthesis of hepatocarcinoma cells by up‐regulating glucose transporters 1 (GLUT1), hexokinase II (HKII) expression and down‐regulating glycogen synthase kinase 3β (GSK3β) expression. Mechanistically, CRKL promoted glucose metabolism of hepatocarcinoma cells via enhancing the CRKL‐PI3K/Akt‐GLUT1/HKII‐glucose uptake, CRKL‐PI3K/Akt‐HKII‐glucose‐lactate production and CRKL‐PI3K/Akt‐Gsk3β‐glycogen synthesis. We demonstrate CRKL facilitates HCC malignancy via enhancing glucose uptake, lactate production and glycogen synthesis through PI3K/Akt pathway. It provides interesting fundamental clues to CRKL‐related carcinogenesis through glucose metabolism and offers novel therapeutic strategies for hepatocarcinoma. John Wiley and Sons Inc. 2021-02-01 2021-03 /pmc/articles/PMC7933966/ /pubmed/33523562 http://dx.doi.org/10.1111/jcmm.16303 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Guo, Chunmei
Gao, Chao
Lv, Xinxin
Zhao, Dongting
Greenaway, Frederick T.
Hao, Lihong
Tian, Yuxiang
Liu, Shuqing
Sun, Ming‐Zhong
CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt
title CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt
title_full CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt
title_fullStr CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt
title_full_unstemmed CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt
title_short CRKL promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating PI3K/Akt
title_sort crkl promotes hepatocarcinoma through enhancing glucose metabolism of cancer cells via activating pi3k/akt
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933966/
https://www.ncbi.nlm.nih.gov/pubmed/33523562
http://dx.doi.org/10.1111/jcmm.16303
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