GLI1 activation is a key mechanism of erlotinib resistance in human non-small cell lung cancer.

GLI1 activation is a key mechanism of erlotinib resistance in human non-small cell lung cancer. Oncol Lett. 2020 Oct;20(4):76 Authors: Dong Z, Wang Y, Ding V, Yan X, Lv Y, Zhong M, Zhu F, Zhao P, He C, Ding F, Shi H Abstract Lung cancer is the leading cause of cancer-associated death worldwide. In recent years, the advancement of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted therapies has provided clinical benefits for lung cancer patients with EGFR mutations. The response to EGFR-TKI varies in patients with lung cancer, and resistance typically develops during the course of the treatment. Therefore, understanding biomarkers which can predict resistance to EGFR-TKI is important. Overexpression of GLI causes activation of the Hedgehog (Hh) signaling pathway and plays a critical role in oncogenesis in numerous types of cancer. In the present study, the role of GLI1 in erlotinib resistance was investigated. GLI1 mRNA and protein expression levels were determined using reverse transcription-quantitative PCR and immunohistochemistry (IHC) in lung cancer cell lines and tumor specimens, respectively. GLI1 mRNA expression levels were found to be positively correlated with the IC50 of erlotinib in 15 non-small cell lung cancer (NSCLC) cell lines. The downregulation of GLI1 using siRNA sensitized lung cancer cells to the erlotinib treatment, whereas the overexpression of GLI1 increased the survival of lung canc...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research