Nerve growth factor receptor increases the tumor growth and metastatic potential of triple-negative breast cancer cells

Wu, Renfei; Li, Koukou; Yuan, Ming-Heng; Luo, Kathy Qian

doi:10.1038/s41388-021-01691-y

Cited by 36 publications

(36 citation statements)

References 36 publications

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“…The amount of immunoreactive bands in MDA-MB-231 cells was much higher than that observed in MDA-MB-453 cells ( Figure 1A ), and similar results were obtained from three different experiments ( Supplementary Figure 1 ). Despite significant levels of the neurotrophin receptor family member p75 have been recently detected in a lung metastatic clone from modified MDA-MB231 cells ( Wu et al, 2021 ), we did not observe in the WB analysis robust levels of p75 ( Supplementary Figures 2A,B ), regardless of the TNBC cell line. These apparent discrepancies might be due to the quite different clones of TNBC cells used.…”

Section: Resultscontrasting

confidence: 87%

Targeting the Nerve Growth Factor Signaling Impairs the Proliferative and Migratory Phenotype of Triple-Negative Breast Cancer Cells

Donato

Galasso

Giovannelli

et al. 2021

Front. Cell Dev. Biol.

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Triple-negative breast cancer is a heterogeneous disease that still lacks specific therapeutic approaches. The identification of new biomarkers, predictive of the disease’s aggressiveness and pharmacological response, is a challenge for a more tailored approach in the clinical management of patients. Nerve growth factor, initially identified as a key factor for neuronal survival and differentiation, turned out to be a multifaceted molecule with pleiotropic effects in quite divergent cell types, including cancer cells. Many solid tumors exhibit derangements of the nerve growth factor and its receptors, including the tropomyosin receptor kinase A. This receptor is expressed in triple-negative breast cancer, although its role in the pathogenesis and aggressiveness of this disease is still under investigation. We now report that triple-negative breast cancer-derived MDA-MB-231 and MDA-MB-453 cells express appreciable levels of tropomyosin receptor kinase A and release a biologically active nerve growth factor. Activation of tropomyosin receptor kinase by nerve growth factor treatment positively affects the migration, invasion, and proliferation of triple-negative breast cancer cells. An increase in the size of triple-negative breast cancer cell spheroids is also detected. This latter effect might occur through the nerve growth factor-induced release of matrix metalloproteinase 9, which contributes to the reorganization of the extracellular matrix and cell invasiveness. The tropomyosin receptor kinase A inhibitor GW441756 reverses all these responses. Co-immunoprecipitation experiments in both cell lines show that nerve growth factor triggers the assembly of the TrkA/β1-integrin/FAK/Src complex, thereby activating several downstream effectors. GW441756 prevents the complex assembly induced by nerve growth factor as well as the activation of its dependent signaling. Pharmacological inhibition of the tyrosine kinases Src and FAK (focal adhesion kinase), together with the silencing of β1-integrin, shows that the tyrosine kinases impinge on both proliferation and motility, while β1-integrin is needed for motility induced by nerve growth factor in triple-negative breast cancer cells. The present data support the key role of the nerve growth factor/tropomyosin receptor kinase A pathway in triple-negative breast cancer and offer new hints in the diagnostic and therapeutic management of patients.

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Section: Resultscontrasting

confidence: 87%

Targeting the Nerve Growth Factor Signaling Impairs the Proliferative and Migratory Phenotype of Triple-Negative Breast Cancer Cells

Donato

Galasso

Giovannelli

et al. 2021

Front. Cell Dev. Biol.

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“…For example, ZEB1 controls inflammatory factor IL6, IL8 and IL1β production [ 44 , 45 ], which can induce cancer metastasis. ZEB1 also can activate signaling pathways associated with tumor metastasis, including PI3K/AKT and WNT5a [ 46 , 47 ]. It’s worth to investigate the targets of ZEB1 regulating by cooperation of METTL14, YHTDF2, ARRDC4, TCF4 and HuR leads to elevation of invasiveness and migration of colorectal cancer cells in the future study.…”

Section: Discussionmentioning

confidence: 99%

TCF4 and HuR mediated-METTL14 suppresses dissemination of colorectal cancer via N6-methyladenosine-dependent silencing of ARRDC4

et al. 2021

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Metastasis remains the major obstacle to improved survival for colorectal cancer (CRC) patients. Dysregulation of N6-methyladenosine (m6A) is causally associated with the development of metastasis through poorly understood mechanisms. Here, we report that METTL14, a key component of m6A methylation, is functionally related to the inhibition of ARRDC4/ZEB1 signaling and to the consequent suppression of CRC metastasis. We unveil METTL14-mediated m6A modification profile and identify ARRDC4 as a direct downstream target of METTL14. Knockdown of METTL14 significantly enhanced ARRDC4 mRNA stability relying on the “reader” protein YHTDF2 dependent manner. Moreover, we demonstrate that TCF4 can induce METTL14 protein expression, and HuR suppress METTL14 expression by directly binding to its promoter. Clinically, our results show that decreased METTL14 is correlated with poor prognosis and acts as an independent predictor of CRC survival. Collectively, our findings propose that METTL14 functions as a metastasis suppressor, and define a novel signaling axis of TCF4/HuR-METTL14-YHTDF2-ARRDC4-ZEB1 in CRC, which might be potential therapeutic targets for CRC.

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“…IL1RL2 is associated with the TEM and metastasis in breast cancer [32]. Nerve growth factor receptor (NGFR) is a member of the neurotrophin receptor family [33]. This gene induces apoptosis and is involved in injury, nervous system development and regeneration.…”

Section: Discussionmentioning

confidence: 99%

Development of an immune-related gene prognostic risk model and identification of an Immune infiltration signature in the tumor microenvironment of colon cancer

Hao

Meng

et al. 2022

Preprint

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Background: Colon cancer is a common and highly malignant tumor. Its incidence is increasing rapidly with poor prognosis. At present, immunotherapy is a rapidly developing treatment for colon cancer. The aim of this study was to construct a prognostic risk model based on immune genes for early diagnosis and accurate prognostic prediction of colon cancer.Results: A total of 477 DE immune genes (180 up-regulated and 297 down-regulated) were detected. We developed and validated twelve immune gene models for colon cancer, including SLC10A2, FABP4, FGF2, CCL28, IGKV1-6, IGLV6-57, ESM1, UCN, UTS2, VIP, IL1RL2, NGFR. The model was proved to be an independent prognostic variable with good prognostic ability. A total of 68 DE TFs (40 up-regulated and 23 down-regulated) were obtained. The regulation network between TF and immune genes was plotted by using TF as source node and immune genes as target node. In addition, Macrophage, Myeloid Dendritic cell and CD4+ T cell increased with the increase of risk score.Conclusions: We developed and validated twelve immune gene models for colon cancer, including SLC10A2, FABP4, FGF2, CCL28, IGKV1-6, IGLV6-57, ESM1, UCN, UTS2, VIP, IL1RL2, NGFR. This model can be used as a tool variable to predict the prognosis of colon cancer.

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Nerve growth factor receptor increases the tumor growth and metastatic potential of triple-negative breast cancer cells

Cited by 36 publications

References 36 publications

Targeting the Nerve Growth Factor Signaling Impairs the Proliferative and Migratory Phenotype of Triple-Negative Breast Cancer Cells

Targeting the Nerve Growth Factor Signaling Impairs the Proliferative and Migratory Phenotype of Triple-Negative Breast Cancer Cells

TCF4 and HuR mediated-METTL14 suppresses dissemination of colorectal cancer via N6-methyladenosine-dependent silencing of ARRDC4

Development of an immune-related gene prognostic risk model and identification of an Immune infiltration signature in the tumor microenvironment of colon cancer

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