Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer
Objective: Triple negative breast cancer (TNBC) is known to have aggressive clinical course and a high risk of recurrence. Given the lack of effective targeted therapy options, paclitaxel-based chemotherapy is still the primary option for TNBC patients. However, patients who fail to achieve a comple...
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doaj-c25a981761a246d89a30d845b8fb55d42021-03-04T07:34:02ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-03-011110.3389/fonc.2021.535230535230Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast CancerShanshan Sun0Hao Wu1Xiaohong Wu2Zilong You3Yang Jiang4Xiaoshuan Liang5Zhuo Chen6Ye Zhang7Wei Wei8Yongdong Jiang9Yanbo Chen10Yanni Song11Da Pang12Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaSino-Russian Medical Research Center, Heilongjiang Academy of Medical Sciences, Harbin, ChinaDepartment of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Pathology, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Anesthesiology, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Anesthesiology, Ningbo Medical Treatment Center Li Huili Hospital, Ningbo, ChinaDepartment of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaDepartment of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, ChinaObjective: Triple negative breast cancer (TNBC) is known to have aggressive clinical course and a high risk of recurrence. Given the lack of effective targeted therapy options, paclitaxel-based chemotherapy is still the primary option for TNBC patients. However, patients who fail to achieve a complete response during neoadjuvant chemotherapy may be mainly due to sensitivity and resistance to chemotherapy. Thus, we concentrated the present research on the role of PGK1 in the sensitivity to paclitaxel treatment and the possible underlying mechanisms in TNBC.Methods: After exposure to paclitaxel, a cell viability analysis was made to investigate the influence of PGK1 silencing on cell death. The effect of PGK1 on apoptosis induced by paclitaxel treatment was examined in vitro by flow cytometry cell apoptosis assays. Western blotting was performed to examine the impact of PGK1 on paclitaxel-induced apoptosis. The correlation of PGK1 with apoptosis-associated protein X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) was analyzed in 39 specimens by immunohistochemistry analysis.Results: We observed that silencing PGK1 sensitized triple-negative breast cancer (TNBC) cell lines to paclitaxel treatment as a result of increased drug-induced apoptosis. Furthermore, mechanistic investigations suggested that XAF1 was increased in PGK1-knockdown cells along with the expression of the apoptotic proteins including cleaved caspase-3 and Bax. Immunohistochemistry analysis showed that PGK1 was negatively related to XAF1. Moreover, we found that downregulation of XAF1 reduced paclitaxel-induced apoptosis in PGK1-silenced triple-negative cell lines.Conclusion: Our results identified PGK1 as a potential biomarker for the treatment of TNBC, and inhibition of PGK1 expression might represent a novel strategy to sensitize TNBC to paclitaxel treatment.https://www.frontiersin.org/articles/10.3389/fonc.2021.535230/fullPGK1triple-negative breast cancerpaclitaxelsensitivitychemotherapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shanshan Sun Hao Wu Xiaohong Wu Zilong You Yang Jiang Xiaoshuan Liang Zhuo Chen Ye Zhang Wei Wei Yongdong Jiang Yanbo Chen Yanni Song Da Pang |
spellingShingle |
Shanshan Sun Hao Wu Xiaohong Wu Zilong You Yang Jiang Xiaoshuan Liang Zhuo Chen Ye Zhang Wei Wei Yongdong Jiang Yanbo Chen Yanni Song Da Pang Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer Frontiers in Oncology PGK1 triple-negative breast cancer paclitaxel sensitivity chemotherapy |
author_facet |
Shanshan Sun Hao Wu Xiaohong Wu Zilong You Yang Jiang Xiaoshuan Liang Zhuo Chen Ye Zhang Wei Wei Yongdong Jiang Yanbo Chen Yanni Song Da Pang |
author_sort |
Shanshan Sun |
title |
Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer |
title_short |
Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer |
title_full |
Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer |
title_fullStr |
Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer |
title_full_unstemmed |
Silencing of PGK1 Promotes Sensitivity to Paclitaxel Treatment by Upregulating XAF1-Mediated Apoptosis in Triple-Negative Breast Cancer |
title_sort |
silencing of pgk1 promotes sensitivity to paclitaxel treatment by upregulating xaf1-mediated apoptosis in triple-negative breast cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-03-01 |
description |
Objective: Triple negative breast cancer (TNBC) is known to have aggressive clinical course and a high risk of recurrence. Given the lack of effective targeted therapy options, paclitaxel-based chemotherapy is still the primary option for TNBC patients. However, patients who fail to achieve a complete response during neoadjuvant chemotherapy may be mainly due to sensitivity and resistance to chemotherapy. Thus, we concentrated the present research on the role of PGK1 in the sensitivity to paclitaxel treatment and the possible underlying mechanisms in TNBC.Methods: After exposure to paclitaxel, a cell viability analysis was made to investigate the influence of PGK1 silencing on cell death. The effect of PGK1 on apoptosis induced by paclitaxel treatment was examined in vitro by flow cytometry cell apoptosis assays. Western blotting was performed to examine the impact of PGK1 on paclitaxel-induced apoptosis. The correlation of PGK1 with apoptosis-associated protein X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) was analyzed in 39 specimens by immunohistochemistry analysis.Results: We observed that silencing PGK1 sensitized triple-negative breast cancer (TNBC) cell lines to paclitaxel treatment as a result of increased drug-induced apoptosis. Furthermore, mechanistic investigations suggested that XAF1 was increased in PGK1-knockdown cells along with the expression of the apoptotic proteins including cleaved caspase-3 and Bax. Immunohistochemistry analysis showed that PGK1 was negatively related to XAF1. Moreover, we found that downregulation of XAF1 reduced paclitaxel-induced apoptosis in PGK1-silenced triple-negative cell lines.Conclusion: Our results identified PGK1 as a potential biomarker for the treatment of TNBC, and inhibition of PGK1 expression might represent a novel strategy to sensitize TNBC to paclitaxel treatment. |
topic |
PGK1 triple-negative breast cancer paclitaxel sensitivity chemotherapy |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.535230/full |
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