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  3. Chemotherapy-induced executioner caspase activation increases breast cancer malignancy through epigenetic de-repression of CDH12

Chemotherapy-induced executioner caspase activation increases breast cancer malignancy through epigenetic de-repression of CDH12

  • Oncogenesis. 2023 Jun 24;12(1):34. doi: 10.1038/s41389-023-00479-x.
Yuxing Wang 1,  Ru Wang 1,  Xiaohe Liu 1,  Menghao Liu 1,  Lili Sun 2,  Xiaohua Pan 3,  Huili Hu 1 4,  Baichun Jiang 1,  Yongxin Zou 1,  Qiao Liu 1,  Yaoqin Gong 1,  Molin Wang 5,  Gongping Sun 6
Affiliations

Affiliations

  • 1 Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
  • 2 Key Laboratory of Experimental Teratology, Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
  • 3 Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
  • 4 Department of Systems Biomedicine and Research Center of Stem Cell and Regenerative Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
  • 5 Key Laboratory of Experimental Teratology, Ministry of Education, Institute of Molecular Medicine and Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China. wml@sdu.edu.cn.
  • 6 Key Laboratory of Experimental Teratology, Ministry of Education, Department of Histology and Embryology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China. sgp@sdu.edu.cn.
PMID: 37355711 DOI: 10.1038/s41389-023-00479-x
Abstract

Cancer relapse and metastasis are major obstacles for effective treatment. One important mechanism to eliminate Cancer cells is to induce Apoptosis. Activation of executioner caspases is the key step in Apoptosis and was considered "a point of no return". However, in recent years, accumulating evidence has demonstrated that cells can survive executioner Caspase activation in response to apoptotic stimuli through a process named anastasis. Here we show that breast Cancer cells that have survived through anastasis (anastatic cells) after exposure to chemotherapeutic drugs acquire enhanced proliferation and migration. Mechanistically, cadherin 12 (CDH12) is persistently upregulated in anastatic cells and promotes breast Cancer malignancy via activation of ERK and CREB. Moreover, we demonstrate that executioner Caspase activation induced by chemotherapeutic drugs results in loss of DNA methylation and repressive histone modifications in the CDH12 promoter region, leading to increased CDH12 expression. Our work unveils the mechanism underlying anastasis-induced enhancement in breast Cancer malignancy, offering new therapeutic targets for preventing post-chemotherapy Cancer relapse and metastasis.

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