Polarity protein Par3 sensitizes breast cancer to paclitaxel by promoting cell cycle arrest

Abstract

Purpose Paclitaxel, belongs to tubulin-binding agents (TBAs), showed a great e cacy against breast cancer via stabilizing microtubules. Drug resistance limits its clinical application. Here we aimed to explore a role of Polarity protein Par3 in improving paclitaxel effectiveness.Methods Breast cancer specimens from 45 patients were collected to study the relationship between Par3 expression and paclitaxel e cacy. The Kaplan-Meier method was used for survival analysis. Cell viability was measured in breast cancer cells (SK-BR-3 and T-47D) with Par3 over-expression or knockdown. The ow cytometry assays were performed to measure cell apoptosis and cell cycle. BrdU incorporation assay and Hoechst 33258 staining were performed to measure cell proliferation and cell apoptosis, respectively. Immuno uorescence was used to detect microtubule structures. Results Par3 expression is associated with good response of paclitaxel in breast cancer patients. Consistently, Par3 overexpression signi cantly sensitizes breast cancer cells to paclitaxel by promoting cell apoptosis and reducing cell proliferation. In Par3 overexpressing cells upon paclitaxel treatment, we observed intensi ed cell cycle arrests at metaphase. Further exploration showed that Par3 overexpression stabilizes microtubules of breast cancer cells in response to paclitaxel, and resists to microtubules instability induced by nocodazole, a microtubule-depolymerizing agent. Conclusion Par3 facilitates polymeric forms of tubulin and stabilizes microtubule structure, which aggravates paclitaxel-induced delay at the metaphase-anaphase transition, leading to proliferation inhibition and apoptosis of breast cancer cells. Par3 has a potential role in sensitizing breast cancer cells to paclitaxel, which may provide a more precise assessment of individual treatment and novel therapeutic targets.

Development of a prognostic model for lung adenocarcinoma polarity‐related genes and analysis of immune landscape

“…40,41 Some polarity-related genes have been found to repress cancer cell proliferation and trigger apoptosis through cell cycle regulation. 42 DNA replication is the fundamental process of accurately replicating and transferring genetic information, which is essential for normal cell function and genetic stability. 43 DNA replication changes are important markers observed in multiple cancer types, like LUAD, liver cancer, and gastric cancer.…”

Research Progress of Natural Drugs for Breast Cancer in the Past 30 Years Based on Bibliometric and Knowledge Graph Analysis

“…Oral administration cannot be achieved, and so it can only be administered intravenously. Improving the water solubility of paclitaxel and increasing its specificity is currently difficult [57].…”

Cell polarity changes in cancer initiation and progression

“…Other examples illustrate the role of polarity protein in tumor cell sensitivity to treatment. For instance, Par3 expression further increases microtubule stabilization upon paclitaxel treatment favoring cell cycle arrest and apoptosis ( Zhao et al, 2022 ). This may explain why the expression level of Par3 in breast cancer specimens correlates with paclitaxel treatment efficiency.…”