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A peripheral blood-based approach involving vimentin along with AURKA enabled efficient tracking of elusive Oct4/Sox2-expressing disseminated breast cancer stem cells

Debomita Sengupta1, Debanjan Thakur1, Elizabeth Mahapatra1, Salini Das1, Jayanta Chakrabarti2, Sagar Sen3, Sutapa Mukherjee1

1 1Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026, India2 3Director & HoD, Department of Surgical Oncology, Chittaranjan National Cancer Institute, Hazra Campus: 37, S. P. Mukherjee Road, Kolkata-700 026, INDIA, Newtown Campus: Street No. 299, DJ Block, Action Area 1D, Kolkata – 700160, INDIA3 4Department of Surgical Oncology, Chittaranjan National Cancer Institute, Street No. 299, DJ Block, Action Area 1D, Kolkata – 700160, INDIA.

Bioscience Reports · 2026-07-21 · DOI: 10.1042/BSR20253828

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Abstract

Abstract A major impediment in the therapeutic success of breast cancer (BC) arises from the persistence of clinically undetectable breast cancer stem cells (BCSCs) that need addressal by targeting translationally relevant markers to restrain relapse. Aurora kinase A (AURKA), due to its negative prognostic effect, was considered in clinical trials yet showed an unappreciable response, highlighting the need for additional markers. The present study tried exploring AURKA as a tool of relevance to detect the abundance of Oct4/Sox2(octamer-binding transcription factor 4/sex-determining region Y-box 2)-expressing BCSCs. The purpose was to understand the underlying intricacies governing the limited success of AURKA inhibition and to seek an improved relevant marker profile for detecting disseminated BCSCs. Flow cytometry and chromatin immunoprecipitation assay findings correlated Oct4/Sox2/AURKA expression, proposing an Oct4/Sox2 threshold-dependent AURKA induction. Surprisingly, in BC patient blood, Oct4/Sox2+ve cells were apparently lacking AURKA, emphasizing marker profile dynamicity in disseminating BCSCs with transient cell fate alterations. Immunoprecipitation/immunofluorescence results highlighted an interaction of pAURKA with fate-determinant pNUMB, hinting toward the existence of an AURKA/pNUMB axis for mesenchymal fate induction in breast cancer cells. Oct4/Sox2/AURKA+ve cells further expressed vimentin, highlighting a mesenchymal fate in BCSCs as evident from correlated Oct4/Sox2 and vimentin expression in patient blood. Hence, our study indicated an existing Oct4/Sox2/AURKA/pNUMB axis during transient mesenchymal differentiation of BCSCs and subsequently advocated for a peripheral blood-based approach using AURKA and vimentin for tracking BCSCs, thus supporting a co-targeting strategy. Preliminary in vitro intervention using combinatorial targeting of AURKA and vimentin reduced stemness propensities. Based on these interesting observations, further in-depth studies are warranted for clinical validation.

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Debomita Sengupta, Debanjan Thakur, Elizabeth Mahapatra, Salini Das, Jayanta Chakrabarti, Sagar Sen, Sutapa Mukherjee (2026). A peripheral blood-based approach involving vimentin along with AURKA enabled efficient tracking of elusive Oct4/Sox2-expressing disseminated breast cancer stem cells. Bioscience Reports. https://doi.org/10.1042/BSR20253828
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