PPFIBP1 activates NF-κB signaling to enhance chemoresistance of multiple myeloma

Yi Deng; Lanting Chen; Qiguo Zhang; Yinyin Xu

doi:10.1016/j.tranon.2023.101765

PPFIBP1 activates NF-κB signaling to enhance chemoresistance of multiple myeloma

Transl Oncol. 2023 Nov:37:101765. doi: 10.1016/j.tranon.2023.101765. Epub 2023 Aug 22.

Authors

Yi Deng¹, Lanting Chen², Qiguo Zhang³, Yinyin Xu⁴

Affiliations

¹ Department of Oncology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
² Department of Hematology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China.
³ Department of Hematology, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu, China; Department of Hematology, Chuzhou First People's Hospital of Anhui Medical University, Chuzhou, Anhui, China.
⁴ Clinical Laboratory of Yongchuan Hospital, Chongqing Medical University, No.439 Xuanhua Rd, Chongqing 402160, China. Electronic address: xuyinyin@hospital.cqmu.edu.cn.

Abstract

Easily developed chemoresistance is a major characteristic of multiple myeloma (MM) and the main obstacle in curing MM in the clinic, but the key regulators have not been fully identified. In the current study, we find that PPFIA Binding Protein 1 (PPFIBP1) is highly expressed in the plasma cells from MM patients, and higher PPFIBP1 expression predicts poorer outcomes. PPFPIBP1 enhances chemoresistance of MM cells to the treatment of bortezomib (BTZ), a proteasome inhibitor, and manipulation of PPFPIBP1 can alter chemosensitivity of MM cells to BTZ. Mechanistic studies reveal that PPFPIBP1 directly binds and stabilizes RelA, promotes the cyto-nuclear translocation of RelA, and activates NF-κB signaling pathway. Targeting PPFPIBP1 in a xenograft mouse model of MM prohibits tumor growth and prolongs overall survival of mice. Taken together, our findings suggest that PPFIBP1 is a crucial regulator of chemoresistance to PIs in MM cells, and shed light on developing therapeutic strategies to overcome chemoresistance by targeting PPFIBP1.

Keywords: Chemoresistance; Multiple myeloma; NF-κB signaling; PPFIBP1; Phosphorylation.