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Open AccessArticle

Phosphorylation of Sox2 at Threonine 116 is a Potential Marker to Identify a Subset of Breast Cancer Cells with High Tumorigenecity and Stem-Like Features

1
Department of Laboratory Medicine and Pathology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada
2
Department of Oncology, University of Alberta, Edmonton, AB T6G 1Z2, Canada
3
DynaLIFEDX Medical Laboratories, Edmonton, AB T6G 1Z2, Canada
*
Author to whom correspondence should be addressed.
Current address: Department of Internal Medicine, University of Alberta, Edmonton, AB T6G 1Z2, Canada
Cancers 2018, 10(2), 41; https://doi.org/10.3390/cancers10020041
Received: 7 December 2017 / Revised: 17 January 2018 / Accepted: 30 January 2018 / Published: 3 February 2018
(This article belongs to the Special Issue Cancer Biomarkers)
We have previously identified a novel phenotypic dichotomy in breast cancer (BC) based on the response to a SRR2 (Sox2 regulatory region 2) reporter, with reporter responsive (RR) cells being more tumorigenic/stem-like than reporter unresponsive (RU) cells. Since the expression level of Sox2 is comparable between the two cell subsets, we hypothesized that post-translational modifications of Sox2 contribute to their differential reporter response and phenotypic differences. By liquid chromatography-mass spectrometry, we found Sox2 to be phosphorylated in RR but not RU cells. Threonine 116 is an important phosphorylation site, since transfection of the T116A mutant into RR cells significantly decreased the SRR2 reporter luciferase activity and the RR-associated phenotype. Oxidative stress-induced conversion of RU into RR cells was accompanied by Sox2 phosphorylation at T116 and increased Sox2-DNA binding. In a cohort of BC, we found significant correlations between the proportion of tumor cells immuno-reactive with anti-phosphorylated Sox2T116 and a high tumor grade (p = 0.006), vascular invasion (p = 0.001) and estrogen receptor expression (p = 0.032). In conclusion, our data suggests that phosphorylation of Sox2T116 contributes to the tumorigenic/stem-like features in RR cells. Detection of phospho-Sox2T116 may be useful in identifying a small subset of tumor cells carrying stem-like/tumorigenic features in BC. View Full-Text
Keywords: breast cancer; intra-tumoral heterogeneity; Sox2; phosphorylation; immunohistochemistry breast cancer; intra-tumoral heterogeneity; Sox2; phosphorylation; immunohistochemistry
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MDPI and ACS Style

Gupta, N.; Gopal, K.; Wu, C.; Alshareef, A.; Chow, A.; Wu, F.; Wang, P.; Ye, X.; Bigras, G.; Lai, R. Phosphorylation of Sox2 at Threonine 116 is a Potential Marker to Identify a Subset of Breast Cancer Cells with High Tumorigenecity and Stem-Like Features. Cancers 2018, 10, 41. https://doi.org/10.3390/cancers10020041

AMA Style

Gupta N, Gopal K, Wu C, Alshareef A, Chow A, Wu F, Wang P, Ye X, Bigras G, Lai R. Phosphorylation of Sox2 at Threonine 116 is a Potential Marker to Identify a Subset of Breast Cancer Cells with High Tumorigenecity and Stem-Like Features. Cancers. 2018; 10(2):41. https://doi.org/10.3390/cancers10020041

Chicago/Turabian Style

Gupta, Nidhi; Gopal, Keshav; Wu, Chengsheng; Alshareef, Abdulraheem; Chow, Alexandra; Wu, Fang; Wang, Peng; Ye, Xiaoxia; Bigras, Gilbert; Lai, Raymond. 2018. "Phosphorylation of Sox2 at Threonine 116 is a Potential Marker to Identify a Subset of Breast Cancer Cells with High Tumorigenecity and Stem-Like Features" Cancers 10, no. 2: 41. https://doi.org/10.3390/cancers10020041

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