TY - JOUR
T1 - CCL2 promotes metastasis and epithelial–mesenchymal transition of non-small cell lung cancer via PI3K/Akt/mTOR and autophagy pathways
AU - Xu, Hui
AU - Wang, Jin
AU - Al-Nusaif, Murad
AU - Ma, Huipeng
AU - Le, Weidong
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (NSFC 31700853).
Publisher Copyright:
© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.
PY - 2023/10/18
Y1 - 2023/10/18
N2 - In non-small cell lung cancer (NSCLC), metastasis is the most common phenotype, and autophagy plays a vital role in its regulation. However, there are limited data on how autophagy-related genes and metastasis-related genes affect NSCLC progression. Our goal was to identify the genes that regulate autophagy and metastasis in NSCLC, and to assess the underlying mechanisms in this current study. RNA sequencing data from public databases were used to screen differentially expressed autophagy- and metastasis-associated genes. Enrichment analyses and immune correlations were conducted to identify hub genes and potential regulating pathways in NSCLC. In this study, we found that CCL2 expression was highly expressed in NSCLC tissues and high CCL2 level was correlated with strong infiltration in lung tissues from NSCLC patients. Overexpression of CCL2 can enhance the metastasis of NSCLC cells in nude mice. Furthermore, CCL2 activated the PI3K/Akt/mTOR signalling pathway axis, promoted epithelial–mesenchymal transition (EMT), and blocked the autophagic flux in NSCLC cells. Therefore, our results indicate that CCL2 promotes metastasis and EMT of NSCLC via PI3K/Akt/mTOR axis and autophagy signalling pathways. We believe that CCL2 could be a probable target for the diagnosis and therapeutics of NSCLC, and this study may expand our understanding of lung cancer.
AB - In non-small cell lung cancer (NSCLC), metastasis is the most common phenotype, and autophagy plays a vital role in its regulation. However, there are limited data on how autophagy-related genes and metastasis-related genes affect NSCLC progression. Our goal was to identify the genes that regulate autophagy and metastasis in NSCLC, and to assess the underlying mechanisms in this current study. RNA sequencing data from public databases were used to screen differentially expressed autophagy- and metastasis-associated genes. Enrichment analyses and immune correlations were conducted to identify hub genes and potential regulating pathways in NSCLC. In this study, we found that CCL2 expression was highly expressed in NSCLC tissues and high CCL2 level was correlated with strong infiltration in lung tissues from NSCLC patients. Overexpression of CCL2 can enhance the metastasis of NSCLC cells in nude mice. Furthermore, CCL2 activated the PI3K/Akt/mTOR signalling pathway axis, promoted epithelial–mesenchymal transition (EMT), and blocked the autophagic flux in NSCLC cells. Therefore, our results indicate that CCL2 promotes metastasis and EMT of NSCLC via PI3K/Akt/mTOR axis and autophagy signalling pathways. We believe that CCL2 could be a probable target for the diagnosis and therapeutics of NSCLC, and this study may expand our understanding of lung cancer.
UR - http://www.scopus.com/inward/record.url?scp=85174306479&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85174306479&partnerID=8YFLogxK
U2 - 10.1111/cpr.13560
DO - 10.1111/cpr.13560
M3 - Article
C2 - 37850256
AN - SCOPUS:85174306479
SN - 0960-7722
VL - 57
SP - e13560
JO - Cell Proliferation
JF - Cell Proliferation
IS - 3
M1 - e13560
ER -