SEZ6L2 Is an Important Regulator of Drug-Resistant Cells and Tumor Spheroid Cells in Lung Adenocarcinoma
- 주제(키워드) lung adenocarcinoma , distant recurrence , drug resistance , circulating tumor cell , tumor spheroid
- 주제(기타) Medicine, Research & Experimental
- 주제(기타) Pharmacology & Pharmacy
- 설명문(일반) [Lee, Jang-Seok; Kim, Hee Yeon; Won, Bomyi; Kim, Yong-Nyun; Jang, Hyonchol] Natl Canc Ctr, Res Inst, Goyang 10408, South Korea; [Kim, Hee Yeon; Kang, Sang Won] Ewha Womans Univ, Dept Life Sci, Seoul 03760, South Korea; [Won, Bomyi; Jang, Hyonchol] Natl Canc Ctr, Dept Canc Biomed Sci, Grad Sch Canc Sci & Policy, Goyang 10408, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 MDPI
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000175093
- 본문언어 영어
- Published As http://dx.doi.org/10.3390/biomedicines8110500
- PubMed https://pubmed.ncbi.nlm.nih.gov/33202873
초록/요약
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.
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