Netrin-1 Stimulates Migration of Neogenin Expressing Aggressive Melanoma Cells

Untiveros, Gustavo; Raskind, Aleksandr; Linares, Laura; Dotti, Alessandro; Strizzi, Luigi

doi:10.3390/ijms232112751

Cited by 5 publications

(3 citation statements)

References 47 publications

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“…Consequently, either losing receptor activity or increasing NTN1 expression is advantageous for tumour progression. However, depending on the type of NTN-1 receptor expression, cells may be either attracted or repulsed by NTN-1 with DCC and NEO-1 being classic attractive receptors and the UNC family repulsive receptors [52,53]. In addition, the loss of NTN-1 receptors is not arbitrary and can be attributed to particular stages of tumour growth [54].…”

Section: Discussionmentioning

confidence: 99%

Increased Expression Levels of Netrin-1 in Visceral Adipose Tissue during Obesity Favour Colon Cancer Cell Migration

Mentxaka

Gómez-Ambrosi

Neira

et al. 2023

Cancers

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Netrin (NTN)-1, an extracellular matrix protein with a crucial role in inflammation, is dysregulated during obesity (OB) and influences colon cancer (CC) progression. To decipher the mechanisms underlying CC development during obesity, we examined the expression of NTN1 and its receptors in the visceral adipose tissue (VAT) of 74 (25 normal weight (NW)) (16 with CC) and 49 patients with OB (12 with CC). We also evaluated the effect of caloric restriction (CR) on the gene expression levels of Ntn1 and its receptors in the colon from a rat model fed a normal diet. The impact of adipocyte-conditioned media (ACM) from patients with OB and NTN-1 was assessed on the expression levels of neogenin 1(NEO1), deleted in colorectal carcinomas (DCC) and uncoordinated-5 homolog B (UNC5B) in Caco-2 and HT-29 human colorectal cell lines, as well as on Caco-2 cell migration. Increased NTN1 and NEO1 mRNA levels in VAT were due to OB (p < 0.05) and CC (p < 0.001). In addition, an upregulation in the expression levels of DCC and UNC5B in patients with CC (p < 0.01 and p < 0.05, respectively) was observed. Decreased (p < 0.01) Ntn1 levels in the colon from rats submitted to CR were found. In vitro experiments showed that ACM increased DCC (p < 0.05) and NEO1 (p < 0.01) mRNA levels in HT-29 and Caco-2 cell lines, respectively, while UNC5B decreased (p < 0.01) in HT-29. The treatment with NTN-1 increased (p < 0.05) NEO1 mRNA levels in HT-29 cells and DCC (p < 0.05) in both cell lines. Finally, we revealed a potent migratory effect of ACM and NTN-1 on Caco-2 cells. Collectively, these findings point to increased NTN-1 during OB and CC fuelling cancer progression and exerting a strong migratory effect on colon cancer cells.

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Section: Discussionmentioning

confidence: 99%

Increased Expression Levels of Netrin-1 in Visceral Adipose Tissue during Obesity Favour Colon Cancer Cell Migration

Mentxaka

Gómez-Ambrosi

Neira

et al. 2023

Cancers

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“…Melanoma is a highly invasive malignant tumor, with 5-year survival rate below 30% once metastasized, accounting for the majority of deaths from skin cancer [ 1 – 3 ]. The extremely strong drug resistance and relapse trend lead to the insensitivity of melanoma towards chemotherapy, radiotherapy and immunotherapy, as well as failed rehabilitation after surgical treatment [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Ce6-modified Fe ions-doped carbon dots as multifunctional nanoplatform for ferroptosis and photodynamic synergistic therapy of melanoma

Li,

Dou,

Yang

et al. 2024

J Nanobiotechnol

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Background Despite the higher sensitivity of melanoma towards ferroptosis and photodynamic therapy (PDT), the lack of efficient ferroptosis inducers and the poor solubility of photosensitizers restrict their synergistic strategies. With unique advantages, carbon dots (CDs) are expected to serve as innovative building blocks for combination therapy of cancers. Results Herein, an ferroptosis/PDT integrated nanoplatform for melanoma therapy is constructed based on chlorin e6-modified Fe ions-doped carbon dots (Fe-CDs@Ce6). As a novel type of iron-carbon hybrid nanoparticles, the as-prepared Fe-CDs can selectively activate ferroptosis, prevent angiogenesis and inhibit the migration of mouse skin melanoma cells (B16), but have no toxicity to normal cells. The nano-conjugated structures facilitate not only the aqueous dispersibility of Ce6, but also the self-accumulation ability of Fe-CDs@Ce6 within melanoma area without requiring extra targets. Moreover, the therapeutic effects of Fe-CDs@Ce6 are synergistically enhanced due to the increased GSH depletion by PDT and the elevated singlet oxygen (1O2) production efficiency by Fe-CDs. When combined with laser irradiation, the tumor growth can be significantly suppressed by Fe-CDs@Ce6 through cyclic administration. The T2-weighted magnetic resonance imaging (MRI) capability of Fe-CDs@Ce6 also reveals their potentials for cancer diagnosis and navigation therapy. Conclusions Our findings indicate the multifunctionality of Fe-CDs@Ce6 in effectively combining ferroptosis/PDT therapy, tumor targeting and MRI imaging, which enables Fe-CDs@Ce6 to become promising biocompatible nanoplatform for the treatment of melanoma. Graphic Abstract

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“…For example, NTN1 has a neuroprotective role in Parkinson's patients [9], whereas, in colorectal tumors, apoptosis-dependent receptor deletion due to Netrin-1 receptor deficiency exacerbates tumor progression [10]. Upregulation of NTN1 also promotes the growth of various tumor cells, such as melanoma, breast cancer, and liver cancer [11][12][13]; the function of NTNG1 is to increase the migration of ovarian cancer cells [14]. In glioblastoma cells, NTN4 activates the mTOR signaling pathway and promotes cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Netrin Family Genes as Prognostic Markers and Therapeutic Targets for Clear Cell Renal Cell Carcinoma: Netrin-4 Acts through the Wnt/β-Catenin Signaling Pathway

Guo

Wang

et al. 2023

Cancers

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Clear cell renal cell carcinoma (ccRCC, or KIRC) is the most common type of kidney cancer, originating within the renal cortex. The current outcomes for early diagnosis and late treatment of ccRCC are unsatisfactory. Therefore, it is important to explore tumor biomarkers and therapeutic opportunities for ccRCC. In this study, we used bioinformatics methods to systematically evaluate the expression and prognostic value of Netrin family genes in ccRCC. Through our analysis, three potential biomarkers for ccRCC were identified, namely NTNG1, NTNG2, and NTN4. Moreover, we performed in vitro and in vivo experiments to explore the possible biological roles of NTN4 and found that NTN4 could regulate ccRCC development through Wnt/β-catenin signaling. We elucidate the molecular mechanism by which NTN4 modulates β-catenin expression and nuclear translocation to inhibit ccRCC progression, providing a new theoretical basis for developing therapeutic targets for ccRCC. Thus, we suggest that Netrin-related studies may offer new directions for the diagnosis, treatment, and prognosis of ccRCC patients.

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Netrin-1 Stimulates Migration of Neogenin Expressing Aggressive Melanoma Cells

Cited by 5 publications

References 47 publications

Increased Expression Levels of Netrin-1 in Visceral Adipose Tissue during Obesity Favour Colon Cancer Cell Migration

Increased Expression Levels of Netrin-1 in Visceral Adipose Tissue during Obesity Favour Colon Cancer Cell Migration

Ce6-modified Fe ions-doped carbon dots as multifunctional nanoplatform for ferroptosis and photodynamic synergistic therapy of melanoma

Netrin Family Genes as Prognostic Markers and Therapeutic Targets for Clear Cell Renal Cell Carcinoma: Netrin-4 Acts through the Wnt/β-Catenin Signaling Pathway

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