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SEZ6L2 Is an Important Regulator of Drug-Resistant Cells and Tumor Spheroid Cells in Lung Adenocarcinoma

Title
SEZ6L2 Is an Important Regulator of Drug-Resistant Cells and Tumor Spheroid Cells in Lung Adenocarcinoma
Authors
Lee, Jang-SeokKim, Hee YeonWon, BomyiKang, Sang WonKim, Yong-NyunJang, Hyonchol
Ewha Authors
강상원
SCOPUS Author ID
강상원scopus
Issue Date
2020
Journal Title
BIOMEDICINES
ISSN
2227-9059JCR Link
Citation
BIOMEDICINES vol. 8, no. 11
Keywords
lung adenocarcinomadistant recurrencedrug resistancecirculating tumor celltumor spheroid
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Many lung cancer deaths result from relapses in distant organs, such as the brain or bones, after standard chemotherapy. For cancer cells to spread to other organs, they must survive as circulating tumor cells (CTCs) in blood vessels. Thus, reducing distant recurrence after chemotherapy requires simultaneously inhibiting drug resistance and CTC survival. Here, we investigated the molecular pathways and genes that are commonly altered in drug-resistant lung cancer cells and lung tumor spheroid (TS) cells. First, RNA sequencing was performed in drug-resistant cells and TS cells originating from H460 and A549 lung cancer cells. Bioinformatic pathway analysis showed that cell cycle-related pathways were downregulated in drug-resistant cells, and cholesterol biosynthesis-related pathways were upregulated in TS cells. Seizure-related 6 homolog-like 2 (SEZ6L2) was selected as a gene that was commonly upregulated in both drug-resistant cells and TS cells, and that showed elevated expression in samples from lung adenocarcinoma patients. Second, the protein expression of SEZ6L2 was analyzed by flow cytometry. The proportions of SEZ6L2 positive cells among both drug-resistant cells and TS cells was increased. Finally, as SEZ6L2 is a transmembrane protein with an extracellular region, the function of SEZ6L2 was disrupted by treatment with an anti-SEZ6L2 antibody. Treatment with the anti-SEZ6L2 antibody reduced drug resistance and TS formation. Overall, our data showed that SEZ6L2 plays an important role in drug resistance and TS formation and may be a therapeutic target for reducing distant recurrence of lung adenocarcinoma.
DOI
10.3390/biomedicines8110500
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자연과학대학 > 생명과학전공 > Journal papers
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