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Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
Published on: September 20, 2024
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SPP1-SRD5A3 signaling axis regulated lymph node metastasis by activating Mucin type O glycan biosynthesis
Tong Xu1,2,3, Wanli Zhang1, Shaobo Gong1
1Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, China.
Summary
Lymph node metastasis (LNM) is driven by SPP1+ macrophages communicating with cancer cells, increasing Steroid 5α-reductase 3 (SRD5A3) expression and promoting cancer spread. Blocking this SPP1-SRD5A3 signaling may offer a new therapeutic strategy for LNM.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Mechanisms
Background:
- Lymph node metastasis (LNM) significantly impacts cancer patient outcomes, yet its regulatory pathways are not fully understood.
- MTOGB is elevated in LNM across various cancers, particularly in epithelial cells, highlighting its role in metastasis.
Purpose of the Study:
- To elucidate the molecular mechanisms driving lymph node metastasis.
- To identify key genes and signaling pathways involved in LNM progression.
Main Methods:
- Single-cell RNA sequencing to identify epithelial cell subpopulations and differentiation trajectories.
- Differential gene expression analysis and gene set enrichment analysis.
- In vitro and in vivo experiments to validate the role of identified genes and pathways, including gene knockdown and drug screening.
Main Results:
- Identified a specific epithelial cell subpopulation (EC4) and six crucial genes involved in LNM.
- Steroid 5α-reductase 3 (SRD5A3) expression positively correlates with LNM stage; its knockdown inhibits metastasis.
- Nilotinib effectively reduces cancer cell metastasis by inhibiting SRD5A3.
- SPP1+ macrophages enhance SOX4/SRD5A3 expression and cancer cell metastasis via cell communication, an effect dependent on SPP1.
Conclusions:
- The SPP1-SRD5A3 signaling pathway is a critical driver of lymph node metastasis.
- Targeting the SPP1-SRD5A3 axis presents a potential therapeutic strategy for inhibiting cancer metastasis.
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