Int J Biol Sci 2021; 17(13):3538-3553. doi:10.7150/ijbs.63430 This issue

Research Paper

CCNB2/SASP/Cathepsin B & PGE2 Axis Induce Cell Senescence Mediated Malignant Transformation

Ying Wang1#, Hanbing Zhang2#, Minglei Wang3#, Jing He4#, Hui Guo2✉, Lihua Li1✉, Jie Wang2✉

1. Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China.
2. Department of Neurosurgery, Shanghai Deji Hospital, Qingdao University, Shanghai 200331, China.
3. Department of Neurosurgery, PuTuo District People's Hospital, Shanghai 200060, China.
4. Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Wang Y, Zhang H, Wang M, He J, Guo H, Li L, Wang J. CCNB2/SASP/Cathepsin B & PGE2 Axis Induce Cell Senescence Mediated Malignant Transformation. Int J Biol Sci 2021; 17(13):3538-3553. doi:10.7150/ijbs.63430. Available from

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Graphic abstract

Glioma is the most frequent and aggressive adult brain tumor with maximum mortality. However, the gene alteration and mechanism underlying malignant transformation of glioma remain largely unknown. We aimed to find key factors regulating tumor progression and malignant transformation of glioma. Here we compared the gene expression profiles of 693 glioma patients by HGG vs. LGG model, and identified a key factor CCNB2 for malignant transformation in glioma. CCNB2 induced a senescence-associated secretory phenotype (SASP) of glioma cells, and the malignant progression, such as invasion and excessive proliferation was mediated by secreting SASP cytokines, Cathepsin B and PGE2. These findings demonstrated a previously undiscovered link between senescence, CCNB2/SASP/Cathepsin B & PGE2 axis and malignant transformation in glioma. This might provide novel insights on developing new therapeutic regimens for abrogating aggressiveness of glioma.

Keywords: CCNB2, cell senescence, Senescence-associated secretory phenotype, malignant transformation, glioma