PGAM1 Promotes Glycolytic Metabolism and Paclitaxel Resistance via Pyruvic Acid Production in Ovarian Cancer Cells

被引：14
作者：
Feng, Yan [1 ]
Zhang, Xu [2 ]
Zhang, Songfa [1 ]
Xu, Shanshan [1 ]
Chen, Xiaojing [3 ]
Zhou, Caiyun [1 ]
Xi, Yongmei [1 ]
Xie, Xing [1 ]
Lu, Weiguo [1 ]
机构：
[1] Zhejiang Univ, Womens Hosp, Sch Med, Hangzhou 310006, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Affiliated Hosp 1, Dept Gynecol, Wenzhou 325000, Zhejiang, Peoples R China
[3] Zhejiang Univ, Womens Hosp, Sch Med, Womens Reprod Hlth Lab Zhejiang Prov, Hangzhou 310006, Zhejiang, Peoples R China
来源：
FRONTIERS IN BIOSCIENCE-LANDMARK | 2022年 / 27卷 / 09期
关键词：
Phosphoglycerate mutase 1; paclitaxel resistance; glycolysis; pyruvate; ovarian cancer cell; PROTEOME; BEVACIZUMAB; STATISTICS; EXPRESSION;
D O I：
10.31083/j.fbl2709262
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Background: Enhanced glycolysis occurs in most human cancer cells and is related to chemoresistance. However, detailed mechanisms remain vague. Methods: Using proteinomics analysis, we found that the glycolytic enzyme Phosphoglycerate mutase 1 (PGAM1) was highly expressed in the paclitaxel-resistant ovarian cancer cell line SKOV3-TR30, as compared to its parental cell line SKOV3. Cell Counting Kit-8 proliferation experiment, plasmids and siRNA transfection, pyruvic acid and lactic acid production detection, immunofluorescence staining of functional mitochondria and oxygen consumption rate and extracellular acidification rate measurement were uesd to assess the glycolytic metabolism and paclitaxel resistance in ovarian cancer cells. The expression and prognostic effect of PGAM1 in 180 ovarian cancer patients were analyzed. Results: SKOV3-TR30 cells display higher glycolytic flux and lower mitochondrial function than SKOV3 cells. Down-regulation of PGAM1 in SKOV3-TR30 cells resulted in decreased paclitaxel resistance. Up-regulation of PGAM1 in SKOV3 cells led to enhanced paclitaxel resistance. Analysis of the glycolytic flux revealed that PGAM1-mediated pyruvic acid or lactic acid production could modulate the capabilities of ovarian cancer cell resistance to paclitaxel. Our data also show high expression of PGAM1 as significantly correlated with reduced overall survival and reduced progression free survival in ovarian cancer patients. Conclusions: PGAM1 acts to promote paclitaxel resistance via pyruvic acid and/or lactate production in ovarian cancer cells. Inhibiting PGAM1 may provide a new approach to favorably alter paclitaxel resistance in ovarian cancer.
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页数：13
相关论文
共 34 条
[1]   Cancer of the ovary, fallopian tube, and peritoneum [J].
Berek, Jonathan S. ;
Crum, Christopher ;
Friedlander, Michael .
INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS, 2015, 131 :S111-S122
[2]   Hypoxia signalling controls metabolic demand [J].
Brahimi-Horn, M. Christiane ;
Chiche, Johanna ;
Pouyssegur, Jacques .
CURRENT OPINION IN CELL BIOLOGY, 2007, 19 (02) :223-229
[3]   Incorporation of Bevacizumab in the Primary Treatment of Ovarian Cancer [J].
Burger, Robert A. ;
Brady, Mark F. ;
Bookman, Michael A. ;
Fleming, Gini F. ;
Monk, Bradley J. ;
Huang, Helen ;
Mannel, Robert S. ;
Homesley, Howard D. ;
Fowler, Jeffrey ;
Greer, Benjamin E. ;
Boente, Matthew ;
Birrer, Michael J. ;
Liang, Sharon X. .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (26) :2473-2483
[4]  
Chao M, 2016, ELIFE, V5, DOI [10.7754/eLife.15691, 10.7554/eLife.15691]
[5]   Characterization of the first described mutation of human red blood cell phosphoglycerate mutase [J].
de Atauri, P ;
Repiso, A ;
Oliva, B ;
Vives-Corrons, JL ;
Climent, F ;
Carreras, J .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2005, 1740 (03) :403-410
[6]   Akt stimulates aerobic glycolysis in cancer cells [J].
Elstrom, RL ;
Bauer, DE ;
Buzzai, M ;
Karnauskas, R ;
Harris, MH ;
Plas, DR ;
Zhuang, HM ;
Cinalli, RM ;
Alavi, A ;
Rudin, CM ;
Thompson, CB .
CANCER RESEARCH, 2004, 64 (11) :3892-3899
[7]   Target discovery in small-molecule cell-based screens by in situ proteome reactivity profiling [J].
Evans, MJ ;
Saghatelian, A ;
Sorensen, EJ ;
Cravatt, BF .
NATURE BIOTECHNOLOGY, 2005, 23 (10) :1303-1307
[8]   Weakened spindle checkpoint with reduced BubR1 expression in paclitaxel-resistant ovarian carcinoma cell line SKOV3-TR30 [J].
Fu, Yunfeng ;
Ye, Dafeng ;
Chen, Huaizeng ;
Lu, Weiguo ;
Ye, Feng ;
Xie, Xing .
GYNECOLOGIC ONCOLOGY, 2007, 105 (01) :66-73
[9]   Correlation of expression levels of ANXA2, PGAM1, and CALR with glioma grade and prognosis [J].
Gao, Huasong ;
Yu, Bin ;
Yan, Yaohua ;
Shen, Jianhong ;
Zhao, Sanhu ;
Zhu, Jianhong ;
Qin, Wenxin ;
Gao, Yilu .
JOURNAL OF NEUROSURGERY, 2013, 118 (04) :846-853
[10]   Why do cancers have high aerobic glycolysis? [J].
Gatenby, RA ;
Gillies, RJ .
NATURE REVIEWS CANCER, 2004, 4 (11) :891-899
1234