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

作者全名："Deng, Yi; Chen, Lanting; Zhang, Qiguo; Xu, Yinyin"

作者地址："[Deng, Yi] Chongqing Med Univ, Yongchuan Hosp, Dept Oncol, Chongqing, Peoples R China; [Chen, Lanting] Chongqing Med Univ, Yongchuan Hosp, Dept Hematol, Chongqing, Peoples R China; [Zhang, Qiguo] Nanjing Univ, Nanjing Drum Tower Hosp, Dept Hematol, Nanjing, Jiangsu, Peoples R China; [Zhang, Qiguo] Anhui Med Univ, Chuzhou Peoples Hosp 1, Dept Hematol, Chuzhou, Anhui, Peoples R China; [Xu, Yinyin] Chongqing Med Univ, Yongchuan Hosp, Clin Lab, 439 Xuanhua Rd, Chongqing 402160, Peoples R China"

通信作者："Xu, YY (通讯作者)，Chongqing Med Univ, Yongchuan Hosp, Clin Lab, 439 Xuanhua Rd, Chongqing 402160, Peoples R China."

来源：TRANSLATIONAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001067570800001

JCR分区：Q1

影响因子：4.5

年份：2023

卷号：37

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Multiple myeloma; Chemoresistance; PPFIBP1; NF-KB signaling; Phosphorylation

摘要："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-KB 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."

基金机构：National Natural Science Foundation of China [82200218]

基金资助正文："This work was supported by the National Natural Science Foundation of China (82200218, Y Xu)."