Cyr61 decreases Cytarabine chemosensitivity in acute lymphoblastic leukemia cells via NF-κB pathway activation.

Abstract

Elevated Cyr61 levels have been reported in various malignancies. Elevation of Cyr61 protein levels contributes to the proliferation, metastasis, and chemotherapy resistance of malignant cells. Previously, it was discovered that Cyr61 is elevated in both the plasma and the bone marrow supernatants of patients with acute lymphoblastic leukemia (ALL), promoting ALL cell survival. However, the role of Cyr61 in the chemotherapeutic resistance of ALL cells remains unknown. The aim of the current study was to investigate the role of Cyr61 in regulating ALL cell chemosensitivity to Ara‑C. It was found that Cyr61 is overexpressed in bone marrow mononuclear cells from patients with ALL. Increased Cyr61 effectively decreased Ara‑C‑induced apoptosis of ALL cells, and its function was blocked by the use of the anti‑Cyr61 monoclonal antibody 093G9. Furthermore, Cyr61 increased the level of Bcl‑2 in Ara‑C‑treated ALL cells. Mechanistically, it was shown that Cyr61 affected ALL cell resistance to Ara‑C partially via the NF‑κB pathway. Taken together, the present study is the first, to the best of our knowledge, to reveal that Cyr61 is involved in ALL cell resistance through the NF‑κB pathway. The findings support a functional role for Cyr61 in promoting chemotherapy resistance, suggesting that targeting Cyr61 directly or its relevant effector pathways may improve the clinical responses of patients with ALL.

• Authors: Yingping Cao, Conglian Wu, Yanfang Song, Zhen Lin, Yanli Kang, Pingxia Lu, Chenqing Zhang, Qinghua Huang, Taisen Hao, Xianjin Zhu, Jianda Hu
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 43 Issue 2 Pg. 1011-1020 (Feb 2019) ISSN: 1791-244X [Electronic] Greece
• PMID: 30535449 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• BCL2 protein, human
• Cysteine-Rich Protein 61
• NF-kappa B
• Proto-Oncogene Proteins c-bcl-2
• Cytarabine

Topics

• Adolescent
• Adult
• Antimetabolites, Antineoplastic (pharmacology)
• Apoptosis (drug effects)
• Bone Marrow (metabolism, pathology)
• Cell Line, Tumor
• Child
• Cysteine-Rich Protein 61 (genetics, metabolism)
• Cytarabine (pharmacology)
• Female
• Gene Expression Regulation, Leukemic (drug effects)
• Humans
• Male
• NF-kappa B (metabolism)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (diagnosis, genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Young Adult