Version 1
: Received: 4 October 2023 / Approved: 6 October 2023 / Online: 9 October 2023 (15:14:51 CEST)
How to cite:
Sengupta, D.; Thakur, D.; Mahapatra, E.; Das, S.; Sen, S.; Roy, A.; Mukherjee, S. Oct4/Sox2 positive breast cancer stem cell-like cells can be detected and targeted by including AURKA and Vimentin in the combinatorial marker profile. Preprints2023, 2023100364. https://doi.org/10.20944/preprints202310.0364.v1
Sengupta, D.; Thakur, D.; Mahapatra, E.; Das, S.; Sen, S.; Roy, A.; Mukherjee, S. Oct4/Sox2 positive breast cancer stem cell-like cells can be detected and targeted by including AURKA and Vimentin in the combinatorial marker profile. Preprints 2023, 2023100364. https://doi.org/10.20944/preprints202310.0364.v1
Sengupta, D.; Thakur, D.; Mahapatra, E.; Das, S.; Sen, S.; Roy, A.; Mukherjee, S. Oct4/Sox2 positive breast cancer stem cell-like cells can be detected and targeted by including AURKA and Vimentin in the combinatorial marker profile. Preprints2023, 2023100364. https://doi.org/10.20944/preprints202310.0364.v1
APA Style
Sengupta, D., Thakur, D., Mahapatra, E., Das, S., Sen, S., Roy, A., & Mukherjee, S. (2023). Oct4/Sox2 positive breast cancer stem cell-like cells can be detected and targeted by including AURKA and Vimentin in the combinatorial marker profile. Preprints. https://doi.org/10.20944/preprints202310.0364.v1
Chicago/Turabian Style
Sengupta, D., Arindam Roy and Sutapa Mukherjee. 2023 "Oct4/Sox2 positive breast cancer stem cell-like cells can be detected and targeted by including AURKA and Vimentin in the combinatorial marker profile" Preprints. https://doi.org/10.20944/preprints202310.0364.v1
Abstract
Aurora Kinase A being overexpressed in majority of cancers, appear to be an attractive therapeutic target. However, a Phase III clinical trial of Alisertib, a selective AURKA inhibitor, resulted in no better response compared to the comparator arm of chemotherapeutic regimen raising question regarding ability of the same to target the undetectable stem cell functions. In silico analysis indicated regulation of AURKA by the stemness factors Oct4 and Sox2. TCGA data indicated positive correlation of each of the factors with AURKA which were eventually validated in cell lines, patient tissues and blood by flow cytometry along with Oct4 binding on AURKA promoter being detected by ChIP assay. However, indirect immunofluorescence and cell cycle analyses indicated proliferation-independent AURKA functions during asymmetric cell division, a characteristic feature of stem cells. Thorough screening of the AURKA positive cells in patient samples denoted epithelial to mesenchymal transition and significant upregulation of Vimentin, a mesenchymal marker and ABCG2, a drug resistance marker under Oct4 or Sox2 influence. Overall, our study demonstrated combinatorial selection Oct4, Sox2, AURKA, Vimentin and ABCG2 for diagnostics and intervention of circulating breast cancer stem cells as a blood-based, cost-effective and simple approach which will be beneficial in reducing relapse.
Keywords
Oct4; Sox2; AURKA; Vimentin; breast cancer; Alisertib; epithelial to mesenchymal transition; asymmetric cell division; NUMB; stem cell; diagnostics; intervention; chemotherapy
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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