Mechanistic insights into CDCP1 clustering on non-small-cell lung cancer membranes revealed by super-resolution fluorescent imaging

Xiao Qi; Zihao Li; Jinrui Zhang; Hongru Li; Guangxin Zhang; Meng Li; Baofeng Li; Yilin Fu; Mingjun Cai; Hongda Wang; Ti Tong; Jing Gao

doi:10.1016/j.isci.2023.106103

Mechanistic insights into CDCP1 clustering on non-small-cell lung cancer membranes revealed by super-resolution fluorescent imaging

iScience. 2023 Feb 2;26(3):106103. doi: 10.1016/j.isci.2023.106103. eCollection 2023 Mar 17.

Authors

Xiao Qi¹, Zihao Li¹, Jinrui Zhang², Hongru Li^{2

3}, Guangxin Zhang¹, Meng Li¹, Baofeng Li¹, Yilin Fu⁴, Mingjun Cai², Hongda Wang^{2

3

5}, Ti Tong¹, Jing Gao²

Affiliations

¹ Department of Thoracic Surgery, the Second Hospital of Jilin University, Changchun, Jilin 130041, China.
² State Key Laboratory of Electroanalytical Chemistry, Research Center of Biomembranomics, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China.
³ University of Science and Technology of China, Hefei, Anhui 230027, China.
⁴ Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
⁵ Laboratory for Marine Biology and Biotechnology, Qing dao National Laboratory for Marine Science and Technology, Wenhai Road, Aoshanwei, Jimo, Qingdao, Shandong 266237, China.

Abstract

CDCP1 is a transmembrane protein that is involved in a variety of important biological processes and upregulated in a variety of human solid malignancies; however, its spatial distribution and variation at the molecular level remain unclear. To solve this problem, we first analyzed its expression level and prognostic implications in lung cancer. Then, we used super-resolution microscopy to reveal the spatial organization of CDCP1 at different levels, and found that cancer cells generated more and larger CDCP1 clusters than normal cells. Furthermore, we found that CDCP1 can be integrated into larger and denser clusters as functional domains upon activation. Our findings elucidated the significant differences of CDCP1 clustering characteristics between cancer and normal cells, and revealed the relationship between its distribution and function, which will contribute to a comprehensive understanding of its oncogenic mechanism, and will be of great help for the development of CDCP1-targeted drugs for lung cancer.

Keywords: Cancer; Cell biology; Optical imaging.