Anastasis confers ovarian cancer cells increased malignancy through elevated p38 MAPK activation

被引:15
作者
Sun, Lili [1 ]
Yao, Chen [1 ]
Li, Xiaojiao [2 ]
Wang, Yuxing [2 ]
Wang, Ru [2 ]
Wang, Molin [2 ]
Liu, Qiao [2 ]
Montell, Denise J. [3 ]
Shao, Changshun [4 ]
Gong, Yaoqin [2 ]
Sun, Gongping [1 ]
机构
[1] Shandong Univ, Sch Basic Med Sci, Dept Histoembryol, Cheeloo Coll Med,Key Lab Expt Teratology,Minist E, Jinan 250012, Shandong, Peoples R China
[2] Shandong Univ, Inst Mol Med & Genet,Cheeloo Coll Med, Sch Basic Med Sci,Key Lab Expt Teratol, Minist Educ,Key Lab Expt Teratol, Jinan 250012, Shandong, Peoples R China
[3] Univ Calif, Mol Cellular & Dev Biol Dept, Santa Barbara, CA 93106 USA
[4] Soochow Univ, Inst Translat Med, State Key Lab Radiat Med & Protect, Suzhou Med Coll, Suzhou 215123, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
PROTEIN-KINASE; INDUCED ANGIOGENESIS; TUMOR-CELLS; APOPTOSIS; PHOSPHORYLATION; CASPASE-3; EXPRESSION; SURVIVAL; PATHWAY; GROWTH;
D O I
10.1038/s41418-022-01081-1
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
Activation of executioner caspases was once considered as a point of no return in apoptosis. However, in recent years, accumulating evidence has demonstrated that cells can survive executioner caspase activation in response to apoptotic stimuli through a process called anastasis. In this study, we developed a reporter system, mCasExpress, to track mammalian cells that survive executioner caspase activation. We demonstrate that anastatic ovarian cancer cells acquire enhanced migration following their transient exposure to apoptotic stimulus TRAIL or Paclitaxel. Moreover, anastatic cancer cells secrete more pro-angiogenic factors that enable tumor angiogenesis, growth and metastasis. Mechanistically, we demonstrate that activation of p38 MAPK, which occurs in a caspase-dependent manner in response to apoptotic stress to promote anastasis, persists at a higher level in anastatic cancer cells even after removal of apoptotic stimuli. Importantly, p38 is essential for the elevated migratory and angiogenic capacity in the anastatic cells. Our work unveils anastasis as a potential driver of tumor angiogenesis and metastasis.
引用
收藏
页码:809 / 824
页数:16
相关论文
共 50 条
[41]   Mechanisms of the JNK/p38 MAPK signaling pathway in drug resistance in ovarian cancer [J].
Ma, Yu-Ting ;
Li, Chan ;
Shen, Ying ;
You, Wan-Hui ;
Han, Ming-Xuan ;
Mu, Yi-Fan ;
Han, Feng-Juan .
FRONTIERS IN ONCOLOGY, 2025, 15
[42]   Knockdown of Wip1 Enhances Sensitivity to Radiation in HeLa Cells Through Activation of p38 MAPK [J].
Wang, Hong-yong ;
Liu, Zhong-shan ;
Qiu, Ling ;
Guo, Jie ;
Li, Yun-feng ;
Zhang, Jun ;
Wang, Tie-jun ;
Liu, Xiao-dong .
ONCOLOGY RESEARCH, 2015, 22 (04) :225-233
[43]   Triterpenes From Ganoderma Lucidum Induce Autophagy in Colon Cancer Through the Inhibition of p38 Mitogen-Activated Kinase (p38 MAPK) [J].
Thyagarajan, Anita ;
Jedinak, Andrej ;
Nguyen, Hai ;
Terry, Colin ;
Baldridge, Lee Ann ;
Jiang, Jiahua ;
Sliva, Daniel .
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 2010, 62 (05) :630-640
[44]   Panaxydol induces apoptosis through an increased intracellular calcium level, activation of JNK and p38 MAPK and NADPH oxidase-dependent generation of reactive oxygen species [J].
Kim, Joo Young ;
Yu, Su-Jin ;
Oh, Hyun Ju ;
Lee, Ji Young ;
Kim, Yongjin ;
Sohn, Jeongwon .
APOPTOSIS, 2011, 16 (04) :347-358
[45]   EGFR Tyrosine 845 Phosphorylation-Dependent Proliferation and Transformation of Breast Cancer Cells Require Activation of p38 MAPK [J].
Mueller, Kelly L. ;
Powell, Katelyn ;
Madden, Julie M. ;
Eblen, Scott T. ;
Boerner, Julie L. .
TRANSLATIONAL ONCOLOGY, 2012, 5 (05) :327-335
[46]   Induction of ER stress protects gastric cancer cells against apoptosis induced by cisplatin and doxorubicin through activation of p38 MAPK [J].
Feng, Ruo ;
Zhai, Wen Long ;
Yang, Hai Yan ;
Jin, Hui ;
Zhang, Qin Xian .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2011, 406 (02) :299-304
[47]   Baicalin potentiates TRAIL-induced apoptosis through p38 MAPK activation and intracellular reactive oxygen species production [J].
Zhang, Lei ;
Wang, Xia ;
Wang, Ruixue ;
Zheng, Xuelian ;
Li, Na ;
Li, Huannan ;
Cao, Xiaoren ;
Zhou, Bin ;
Lin, Yong ;
Yang, Lan .
MOLECULAR MEDICINE REPORTS, 2017, 16 (06) :8549-8555
[48]   Growth State-Dependent Activation of eNOS in Response to DHA: Involvement of p38 MAPK [J].
Huang, Shiqi ;
Taylor, Carla G. ;
Zahradka, Peter .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (09)
[49]   Endotoxin-induced activation of equine digital vein endothelial cells: Role of p38 MAPK [J].
Brooks, Andrew C. ;
Menzies-Gow, Nicola J. ;
Wheeler-Jones, Caroline ;
Bailey, Simon R. ;
Cunningham, Fiona M. ;
Elliott, Jonathan .
VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY, 2009, 129 (3-4) :174-180
[50]   Tanshinone II A Facilitates Chemosensitivity of Osteosarcoma Cells to Cisplatin via Activation of p38 MAPK Pathway [J].
Xie, Da-ming ;
Li, Zhi-yun ;
Ren, Bing-kai ;
Gong, Rui ;
Yang, Dong ;
Huang, Sheng .
CHINESE JOURNAL OF INTEGRATIVE MEDICINE, 2025, 31 (04) :326-335