ST8SIA1 inhibition sensitizes triple negative breast cancer to chemotherapy via suppressing Wnt/β-catenin and FAK/Akt/mTOR
H Wan, Z Li, H Wang, F Cai, L Wang - Clinical and Translational Oncology, 2021 - Springer
H Wan, Z Li, H Wang, F Cai, L Wang
Clinical and Translational Oncology, 2021•SpringerBackground Chemoresistance is the major cause of therapeutic failure in triple negative
breast cancer (TNBC). In this work, we investigated the molecular mechanism for the
development of TNBC chemoresistance. Methods mRNA and protein levels of ST8SIA1
were analyzed in chemosensitive and chemoresistant TNBC cells and tissues. Proliferation
and survival assays were performed to determine the role of ST8SIA1 in TNBC
chemoresistance. Results We found that ST8SIA1 mRNA and protein levels were increased …
breast cancer (TNBC). In this work, we investigated the molecular mechanism for the
development of TNBC chemoresistance. Methods mRNA and protein levels of ST8SIA1
were analyzed in chemosensitive and chemoresistant TNBC cells and tissues. Proliferation
and survival assays were performed to determine the role of ST8SIA1 in TNBC
chemoresistance. Results We found that ST8SIA1 mRNA and protein levels were increased …
Background
Chemoresistance is the major cause of therapeutic failure in triple negative breast cancer (TNBC). In this work, we investigated the molecular mechanism for the development of TNBC chemoresistance.
Methods
mRNA and protein levels of ST8SIA1 were analyzed in chemosensitive and chemoresistant TNBC cells and tissues. Proliferation and survival assays were performed to determine the role of ST8SIA1 in TNBC chemoresistance.
Results
We found that ST8SIA1 mRNA and protein levels were increased in multiple TNBC cell lines after prolonged exposure to chemotherapeutic drugs. Consistently, retrospective study demonstrated that the majority of TNBC patients who developed chemoresistance displayed upregulation of ST8SIA1. We further found that chemoresistant TNBC cells were more sensitive than chemosensitive cells to ST8SIA1 inhibition in decreasing growth and viability. Consistently, ST8SIA1 inhibition augmented the efficacy of chemotherapy in TNBC cells. Mechanism studies demonstrated that ST8SIA1 inhibition led to suppression of FAK/Akt/mTOR and Wnt/β-catenin signalling pathways.
Conclusions
These findings provide an explanation for the heterogeneity of chemotherapy responses across TNBC individuals and reveal the supportive roles of ST8SIA1in TNBC chemoresistance.
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