AXL, along with PROS1, is overexpressed in papillary thyroid carcinoma and regulates its biological behaviour

Wei, Mingze; Wang, Yizeng; Liu, Yuanchao; Li, Dongyang; He, Xianghui

doi:10.1186/s12957-022-02801-0

Cited by 4 publications

(3 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have demonstrated that Gas6 binds to all three TAM receptors, while PROS1 activates Tyro3 (with high affinity) and Mer, but not AXL [34]. However, recent studies have provided evidence that PROS1 can also activate AXL in tumor cells, thereby promoting tumor cell proliferation and invasiveness [21,35,36]. PROS1 and TAM receptors signaling pathways have been recognized as a crucial negative regulator of the immune system, playing a role in limiting the intensity and duration of immune responses [17,37].…”

Section: Discussionmentioning

confidence: 99%

MICA+ Tumor Cell Upregulated Macrophage-Secreted MMP9 via PROS1-AXL Axis to Induce Tumor Immune Escape in Advanced Hepatocellular Carcinoma (HCC)

Wu,

Li,

Yang

et al. 2024

Cancers

View full text Add to dashboard Cite

Background: tumor-associated macrophages (TAMs) constitute a significant proportion of non-cancerous cells within the intricate tumor microenvironment (TME) of hepatocellular carcinoma (HCC). Understanding the communication between macrophages and tumor cells, as well as investigating potential signaling pathways, holds promise for enhancing therapeutic responses in HCC. Methods: single-cell RNA-sequencing data and bulk RNA-sequencing data were derived from open source databases Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Through this analysis, we elucidated the interactions between MICA+ tumor cells and MMP9+ macrophages, primarily mediated via the PROS1-AXL axis in advanced HCC. Subsequently, we employed a range of experimental techniques including lentivirus infection, recombinant protein stimulation, and AXL inhibition experiments to validate these interactions and unravel the underlying mechanisms. Results: we presented a single-cell atlas of advanced HCC, highlighting the expression patterns of MICA and MMP9 in tumor cells and macrophages, respectively. Activation of the interferon gamma (IFN-γ) signaling pathway was observed in MICA+ tumor cells and MMP9+ macrophages. We identified the existence of an interaction between MICA+ tumor cells and MMP9+ macrophages mediated via the PROS1-AXL axis. Additionally, we found MMP9+ macrophages had a positive correlation with M2-like macrophages. Subsequently, experiments validated that DNA damage not only induced MICA expression in tumor cells via IRF1, but also upregulated PROS1 levels in HCC cells, stimulating macrophages to secrete MMP9. Consequently, MMP9 led to the proteolysis of MICA. Conclusion: MICA+ HCC cells secreted PROS1, which upregulated MMP9 expression in macrophages through AXL receptors. The increased MMP9 activity resulted in the proteolytic shedding of MICA, leading to the release of soluble MICA (sMICA) and the subsequent facilitation of tumor immune escape.

show abstract

Section: Discussionmentioning

confidence: 99%

MICA+ Tumor Cell Upregulated Macrophage-Secreted MMP9 via PROS1-AXL Axis to Induce Tumor Immune Escape in Advanced Hepatocellular Carcinoma (HCC)

Wu,

Li,

Yang

et al. 2024

Cancers

View full text Add to dashboard Cite

show abstract

“…Furthermore, our study reveals that Pros1-Axl plays a signi cant communication role among different cells. Previous research has suggested that Pros1-Axl is involved in regulating thyroid papillary carcinoma cell proliferation and migration, as well as modulating immune-in ammatory responses in brain injury [35,36] . However, there is currently limited research investigating the role of Pros1-Axl in oxidative stress reactions and SCI.…”

Section: Discussionmentioning

confidence: 99%

Revealing the expression characteristics and potential regulatory mechanisms of hub oxidative stress related genes of spinal cord injury

Li,

Tong,

Zhou

et al. 2023

Preprint

View full text Add to dashboard Cite

Spinal cord injury (SCI) induces oxidative stress reactions, exacerbating secondary damage. Moderating oxidative stress after SCI holds paramount significance for alleviating secondary injury. At the same time, comprehensive investigations into the pathogenesis of oxidative stress in SCI remain limited. In this study, we analyzed public datasets to identify differentially expressed oxidative stress-related genes (DEOSRGs) at various post-injury time points, identifying 25 hub oxidative stress-related genes (OSRGs). We also conducted tests and validations to ascertain the temporal expression patterns of some hub genes at both the tissue and single-cell levels. Subsequently, we unveiled the association between these hub genes and immune cell infiltration. Functional and pathway enrichment analyses were conducted on DEOSRGs at distinct time points, revealing alterations in enriched functions and signaling pathways. Additionally, we summarized potential communication signaling characteristics related to oxidative stress among different cells at various time points at the single-cell level, along with associated ligand-receptor pairs. As a subsequent step, we constructed mRNA-miRNA/mRNA-miRNA-lncRNA regulatory networks related to oxidative stress in SCI and analyzed transcription factors associated with hub OSRGs. Finally, leveraging the DSigDB database, we predicted compounds capable of inhibiting eight hub genes, offering potential drugs or molecules for targeted interventions in oxidative stress following SCI. Consequently, this study holds significance for gaining deeper insights into oxidative stress mechanisms after SCI and timely targeted interventions in oxidative stress following SCI.

show abstract

“…Further, Zhu et al demonstrated that ITGA5 overexpression promotes poor prognosis in GAC [ 65 ]. In the PROS pathway, the PROS1 ligand and its receptor AXL are overexpressed in thyroid cancer, while AXL blockade suppresses the invasion of thyroid cancer cells [ 66 ]. Within the TME, the tumor homing of mesenchymal stromal cells is regulated by the MIF-(CD74 + CXCR4) ligand–receptor pair in the MIF pathway [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of single-cell and bulk RNA-sequencing reveals the poor prognostic value of ABCA1 in gastric adenocarcinoma

Shen,

Ke,

Chen

et al. 2023

Discov Onc

View full text Add to dashboard Cite

Purpose ATP-binding cassette A1 (ABCA1) is a potential prognostic marker for various tumor types. However, the biological effects and prognostic value of ABCA1 in gastric adenocarcinoma (GAC) remain unknown. Methods GAC-associated single-cell RNA and bulk RNA-sequencing (bulk-seq) data were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively. The differential expression of ABCA1 between GAC and normal gastric tissues was analyzed based on the bulk-seq data. Additionally, the relationship between ABCA1 expression and various clinicopathological features was explored. Furthermore, Kaplan–Meier survival and Cox regression analyses were performed to establish the prognostic value of ABCA1. The relationships between ABCA1 expression and anti-tumor drug sensitivity and immune checkpoints were also explored. Finally, the biological functions of ABCA1 were evaluated at the single-cell level, and in vitro studies were performed to assess the effects of ABCA1 on GAC cell proliferation and invasion. Results ABCA1 expression is significantly elevated in GAC samples compared with that in normal gastric tissues. Clinical features and survival analysis revealed that high ABCA1 expression is associated with poor clinical phenotypes and prognosis, whereas Cox analysis identified ABCA1 as an independent risk factor for patients with GAC. Furthermore, high ABCA1 expression suppresses sensitivity to various chemotherapeutic drugs, including cisplatin and mitomycin, while upregulating immune checkpoints. ABCA1-overexpressing macrophages are associated with adverse clinical phenotypes in GAC and express unique ligand–receptor pairs that drive GAC progression. In vitro, ABCA1-knockdown GAC cells exhibit significantly inhibited proliferative and invasive properties. Conclusion High ABCA1 expression promotes an adverse immune microenvironment and low survival rates in patients with GAC. Furthermore, ABCA1 and ABCA1-producing macrophages may serve as novel molecular targets in GAC treatment.

show abstract

AXL, along with PROS1, is overexpressed in papillary thyroid carcinoma and regulates its biological behaviour

Cited by 4 publications

References 31 publications

MICA+ Tumor Cell Upregulated Macrophage-Secreted MMP9 via PROS1-AXL Axis to Induce Tumor Immune Escape in Advanced Hepatocellular Carcinoma (HCC)

MICA+ Tumor Cell Upregulated Macrophage-Secreted MMP9 via PROS1-AXL Axis to Induce Tumor Immune Escape in Advanced Hepatocellular Carcinoma (HCC)

Revealing the expression characteristics and potential regulatory mechanisms of hub oxidative stress related genes of spinal cord injury

Integrated analysis of single-cell and bulk RNA-sequencing reveals the poor prognostic value of ABCA1 in gastric adenocarcinoma

Contact Info

Product

Resources

About