COL8A1 Promotes NSCLC Progression Through IFIT1/IFIT3-Mediated EGFR Activation

Xiangyi Zan; Shuyan Li; Shixiong Wei; Liping Gao; Lanting Zhao; Xiaoxia Yan; Yan Zhao; Junnian Shi; Yuping Wang; Rong Liu; Yuanyi Zhang; Yixin Wan; Yongning Zhou

doi:10.3389/fonc.2022.707525

COL8A1 Promotes NSCLC Progression Through IFIT1/IFIT3-Mediated EGFR Activation

Front Oncol. 2022 Feb 24:12:707525. doi: 10.3389/fonc.2022.707525. eCollection 2022.

Authors

Xiangyi Zan^{1

2

3}, Shuyan Li⁴, Shixiong Wei⁵, Liping Gao¹, Lanting Zhao¹, Xiaoxia Yan¹, Yan Zhao¹, Junnian Shi¹, Yuping Wang^{2

3}, Rong Liu^{2

3}, Yuanyi Zhang⁶, Yixin Wan¹, Yongning Zhou^{2

3}

Affiliations

¹ Department of Pneumology, The Second Hospital of Lanzhou University, Lanzhou, China.
² Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China.
³ Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China.
⁴ Department of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, China.
⁵ Biological Science, University of California, Davis, Davis, CA, United States.
⁶ Clinical Medicine, University of South China, Hengyang, China.

Abstract

Activation of EGFR is a major risk factor for non-small cell lung cancer (NSCLC). Understanding the molecular events promoting EGFR activation can help us gain more insights into the progression of NSCLC. In this study, we demonstrate that collagen type VIII alpha 1 chain (COL8A1), an extracellular matrix component, was overexpressed in NSCLC. In NSCLC cells, knockdown of COL8A1 suppressed cell growth, cycle progression, and migration, and induced cell apoptosis. While COL8A1 overexpression promoted cell proliferation and inhibited cell apoptosis. In addition, we found that COL8A1 depletion reduced interferon response signaling and downregulated (IFIT1) and interferon-induced proteins with tetratricopeptide repeats 3 (IFIT3). Moreover, we indicated that COL8A1 could upregulate IFIT1 and IFIT3 mediated EGFR activation in vitro and in vivo. Lastly, there was a positive correlation among COL8A1, IFIT1, and IFIT3 expression, and EGFR activity in patients with NSCLC. Overall, our data demonstrate that COL8A1 contributes to NSCLC proliferation and invasion through EGFR activation, dependent on IFIT1 and IFIT3 expression.

Keywords: COL8A1; EGFR; IFIT1; IFIT3; NSCLC.