Open AccessProfilin 1 induces drug resistance through Beclin1 complex‐mediated autophagy in multiple myeloma
Author(s) -
Lu Yichen,
Wang Ya,
Xu He,
Shi Chen,
Jin Fengyan,
Li Wei
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13711
Subject(s) - autophagy , gene knockdown , downregulation and upregulation , microbiology and biotechnology , cancer research , phenotype , bortezomib , biology , chemistry , gene , multiple myeloma , apoptosis , immunology , genetics
Autophagy plays an important role in multiple myeloma ( MM ) for homeostasis, survival and drug resistance, but which genes participate in this process is unclear. We identified several cytoskeleton genes upregulated in MM patients by gene expression profiling ( GEP ) datasets; in particular, patients with high profilin 1 ( PFN 1) expression had poor prognosis in MM . In vitro, overexpressed PFN 1 promotes proliferation and bortezomib ( BTZ ) resistance in MM cells. Further study indicated overexpression of PFN 1 significantly promoted the process of autophagy and induced BTZ resistance in MM . Otherwise, knockdown of PFN 1 blocked autophagy and sensitized MM to BTZ . Co‐immunoprecipitation in MM cells indicated that PFN 1 could bind Beclin1 complex and promote the initiation of autophagy. Inhibition of autophagy by blocking the formation of Beclin1 complex could reverse the phenotype of BTZ resistance in MM . Our findings suggested that PFN 1 could promote autophagy through taking part in Beclin1 complex and contribute to BTZ resistance, which may become a novel molecular target in the therapy of MM .