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E3 ubiquitin ligases Cbl‐b and c‐Cbl downregulate PD ‐L1 in EGFR wild‐type non‐small cell lung cancer
Author(s) -
Wang Shuo,
Xu Ling,
Che Xiaofang,
Li Ce,
Xu Lu,
Hou Kezuo,
Fan Yibo,
Wen Ti,
Qu Xiujuan,
Liu Yunpeng
Publication year - 2018
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12985
Subject(s) - ubiquitin , downregulation and upregulation , cancer research , mapk/erk pathway , a549 cell , protein kinase b , chemistry , lung cancer , cell , signal transduction , microbiology and biotechnology , biology , medicine , biochemistry , gene
Anti‐ PD ‐1/ PD ‐L1 therapies have demonstrated prominent clinical effects in the treatment of non‐small cell lung cancer ( NSCLC ). However, limited understanding of the regulatory mechanisms of PD ‐L1 has become one of the biggest challenges for further improving efficacy. In this study, we observed that in wild‐type EFGR cell lines A549 and H460, the ubiquitin ligases Cbl‐b and c‐Cbl inhibit PD ‐L1 by inactivating STAT , AKT , and ERK signaling. MiR‐181a and miR‐940 were screened and validated to target Cbl‐b and c‐Cbl, respectively. Furthermore, in NSCLC tissues, the expression of Cbl‐b/c‐Cbl is negatively correlated with PD ‐L1 expression. Taken together, these findings indicated a new regulatory mechanism for PD ‐L1 in wild‐type EGFR NSCLC cell lines by Cbl‐b and c‐Cbl.