PKM1 Regulates the Expression of Autophagy and Neuroendocrine Markers in Small Cell Lung Cancer
10.3779/j.issn.1009-3419.2024.102.33
- VernacularTitle:PKM1调控小细胞肺癌自噬与神经内分泌标志物表达
- Author:
TANG CHENCHEN
1
;
JIN YULONG
;
ZHAO PEIYAN
;
TIAN LIN
;
LI HUI
;
YANG CHANGLIANG
;
ZHONG RUI
;
LIU JINGJING
;
MA LIXIA
;
CHENG YING
Author Information
1. 130012 长春,吉林省肿瘤医院生物样本库
- Keywords:
Lung neoplasms;
PKM1;
Autophagy;
Neuroendocrin;
Drug sensitivity
- From:
Chinese Journal of Lung Cancer
2024;27(9):645-653
- CountryChina
- Language:Chinese
-
Abstract:
Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.
