Premium
Upregulation of secreted phosphoprotein 1 affects malignant progression, prognosis, and resistance to cetuximab via the KRAS/MEK pathway in head and neck cancer
Author(s) -
Liu Kai,
Hu Huiying,
Jiang Huanyu,
Liu Chenglei,
Zhang Haidong,
Gong Shanchun,
Wei Dongmin,
Yu Zhenkun
Publication year - 2020
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23245
Subject(s) - cetuximab , head and neck squamous cell carcinoma , kras , cancer research , downregulation and upregulation , biology , gene knockdown , gene silencing , tumor progression , cancer , mek inhibitor , mapk/erk pathway , head and neck cancer , colorectal cancer , apoptosis , signal transduction , biochemistry , genetics , gene
Acquired resistance is a barrier to cetuximab efficacy in patients with head and neck squamous cell carcinoma (HNSCC). Secreted phosphoprotein 1 (SPP1) is involved in various biological processes, including immune responses, cancer progression, and prognosis in many cancers, while little is known in HNSCC. Bioinformatics methods were used to identify candidate genes and further in vivo and in vitro experiments were performed to examine and validate the function of SPP1. We found that SPP1 was upregulated and has been found to have an oncogenic role in HNSCC. We further confirmed that overexpression of SPP1 affected proliferation, migration, invasion, and survival, and inhibited apoptosis, whereas silencing of SPP1 yielded opposite results to those of SPP1 overexpression. In addition, activation of the KRAS/MEK pathway contributed to the SPP1‐induced malignant progression of HNSCC and resistance to cetuximab. Furthermore, SPP1 knockdown or an MEK inhibitor overcame this cetuximab‐resistance pattern. Taken together, our findings for the first time identify the role of SPP1 in tumor promotion, prognostic prediction, and potential therapeutic targeting, as well as resistance to cetuximab in HNSCC.