Abstract
Purpose
To study the expression and intracellular localization of phosphorylase kinase β (PHKβ) protein in colorectal cancers (CRCs), analyze its correlation with clinicopathological features and prognosis, and study the biological roles and mechanism-of-action of PHKβ in CRC cell lines.
Methods
Quantitative polymerase chain reaction (qPCR) and western blot assays were performed to compare the expressions of PHKβ mRNA and protein in CRC tissues and matched normal mucosa. Tissue microarrays and immunohistochemical staining were performed to detect the expression and intracellular location of PHKβ protein and analyze its correlation with the clinicopathological characteristics and prognosis in CRC patients. Proliferation, cell cycle, wound healing, and xenograft models were used to elucidate the potential role of PHKβ in vitro and in vivo.
Results
PHKβ mRNA and protein were found to be overexpressed in CRC tissue compared to the levels in normal mucosa. Positive expression of PHKβ was significantly correlated with TNM stage and distal metastasis, and elevated expression of PHKβ was an independent prognostic factor in patients with CRC. PHKβ knockdown impaired proliferation of CRC in vitro and in vivo and induced cell cycle arrest.
Conclusions
PHKβ affects CRC cell growth and represents a novel prognostic biomarker.
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This work was supported by National Natural Science Foundation of China (Grant No. 81372636 and No. 81302089), the National High Technology Research and Development Program of China (863 Program) (Grant No. SQ2014SFOZD00314), the Shanghai Excellent Young Teachers Program (Grant No. ZZjdyx13074).
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Author declares that he has no conflict of interest.
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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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G. Wang and W. Shen are contributed equally to this article.
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Wang, G., Shen, W., Liu, Cy. et al. Phosphorylase kinase β affects colorectal cancer cell growth and represents a novel prognostic biomarker. J Cancer Res Clin Oncol 143, 971–980 (2017). https://doi.org/10.1007/s00432-017-2362-1
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DOI: https://doi.org/10.1007/s00432-017-2362-1