Comprehensive analysis of the role of Netrin G1 (NTNG1) in hepatocellular carcinoma cells

Gao, Xing; Lin, Yan; Huang, Xi; Lu, Cheng; Luo, Wenfeng; Zeng, Dandan; Li, Yongqiang; Su, Tingshi; Liang, Rong; Ye, Jiazhou

doi:10.1016/j.ejphar.2023.176262

Cited by 2 publications

(3 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Structurally, NGL-1 contains an extracellular region with ten leucin-rich repeats (LRRs), a cysteine-rich capping domain in each LRR end and a C2-type immunoglobulin (Ig) domain. These are followed by a single transmembrane domain and a cytoplasmic domain that interacts with a PDZ binding motif (139,140). It has been shown that NGL-1 mutant mice present hyperactive, anxiolytic-like behavior and impaired learning and memory (40).…”

Section: Discussionmentioning

confidence: 99%

“…Cell adhesion molecules at synaptic sites, such as NGL-1, are known to be multifunctional proteins involved in the coordination of assorted aspects of development, as well as cellular function and plasticity (142). Despite that, only a few studies propose a role for NGL-1 in cancer and in other diseases (29,31,140,143). Analyzing RNAseq data from patients with colon cancer and stomach cancer (available at TCGA) using the algorithm “Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression” (ESTIMATE), Yang et al found that LRRC4C was indicative of an altered TME.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Netrin G1 Ligand is a new stromal immunomodulator that promotes pancreatic cancer

Vendramini-Costa,

Francescone,

Franco-Barraza

et al. 2024

Preprint

View full text Add to dashboard Cite

Understanding pancreatic cancer biology is fundamental for identifying new targets and for developing more effective therapies. In particular, the contribution of the stromal microenvironment to pancreatic cancer tumorigenesis requires further exploration. Here, we report the stromal roles of the synaptic protein Netrin G1 Ligand (NGL-1) in pancreatic cancer, uncovering its pro-tumor functions in cancer-associated fibroblasts and in immune cells. We observed that the stromal expression of NGL-1 inversely correlated with patient overall survival. Moreover, germline knockout (KO) mice for NGL-1 presented decreased tumor burden, with a microenvironment that is less supportive of tumor growth. Of note, tumors from NGL-1 KO mice produced less immunosuppressive cytokines and displayed an increased percentage of CD8+ T cells than those from control mice, while preserving the physical structure of the tumor microenvironment. These effects were shown to be mediated by NGL-1 in both immune cells and in the local stroma, in a TGF-β-dependent manner. While myeloid cells lacking NGL-1 decreased the production of immunosuppressive cytokines, NGL-1 KO T cells showed increased proliferation rates and overall polyfunctionality compared to control T cells. CAFs lacking NGL-1 were less immunosuppressive than controls, with overall decreased production of pro-tumor cytokines and compromised ability to inhibit CD8+ T cells activation. Mechanistically, these CAFs downregulated components of the TGF-β pathway, AP-1 and NFAT transcription factor families, resulting in a less tumor-supportive phenotype. Finally, targeting NGL-1 genetically or using a functionally antagonistic small peptide phenocopied the effects of chemotherapy, while modulating the immunosuppressive tumor microenvironment (TME), rather than eliminating it. We propose NGL-1 as a new local stroma and immunomodulatory molecule, with pro-tumor roles in pancreatic cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Netrin G1 Ligand is a new stromal immunomodulator that promotes pancreatic cancer

Vendramini-Costa,

Francescone,

Franco-Barraza

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…They hypothesized that NTN1 activated downstream signalling pathways in hypoxic HCC cells, causing EMT and the generation of numerous inflammatory mediators, which promote cancer invasion. Moreover, our research team 93 has found that NTNG1 was highly expressed in HCC cell lines and tumour tissues and was positively associated with poorer OS rates. NTNG1 overexpression in HCC cells significantly increased their proliferation, invasion, migration, and EMT, while inhibiting apoptosis.…”

Section: Netrins and Tumoursmentioning

confidence: 99%

Research progress of the netrins and their receptors in cancer

Gao,

Ye,

Huang

et al. 2024

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

Netrins, a family of secreted and membrane‐associated proteins, can regulate axonal guidance, morphogenesis, angiogenesis, cell migration, cell survival, and tumorigenesis. Four secreted netrins (netrin 1, 3, 4 and 5) and two glycosylphosphatidylinositols‐anchored membrane proteins, netrin‐G1 and G2, have been identified in mammals. Netrins and their receptors can serve as a biomarker and molecular therapeutic target for pathological differentiation, diagnosis and prognosis of malignant cancers. We review here the potential roles of the netrins family and their receptors in cancer.

show abstract

Comprehensive analysis of the role of Netrin G1 (NTNG1) in hepatocellular carcinoma cells

Cited by 2 publications

References 40 publications

Netrin G1 Ligand is a new stromal immunomodulator that promotes pancreatic cancer

Netrin G1 Ligand is a new stromal immunomodulator that promotes pancreatic cancer

Research progress of the netrins and their receptors in cancer

Contact Info

Product

Resources

About