PARP3 controls TGFβ and ROS driven epithelial-to-mesenchymal transition and stemness by stimulating a TG2-Snail-E-cadherin axis

Karicheva, Olga; Rodríguez-Vargas, José Manuel; Wadier, Nadége; Martin-Hernandez, Kathline; Vauchelles, Romain; Magroun, Najat; Tissier, Agnès; Schreiber, Valérie; Dantzer, Françoise

doi:10.18632/oncotarget.11627

Cited by 81 publications

(62 citation statements)

References 55 publications

(79 reference statements)

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“…As CSCs seem able to preferentially resist drugs-induced DNA damage [22]. We continued exploring whether NRP-1 is involved in doxorubicin sensitivity via conferring CSCs formation in breast cancer cells.…”

Section: Resultsmentioning

confidence: 99%

VEGF-A/Neuropilin 1 Pathway Confers Cancer Stemness via Activating Wnt/β-Catenin Axis in Breast Cancer Cells

Zhang

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Targeting cancer stem cells (CSCs) is emerging as a promising method for cancer treatment. We previously indicated that knockdown of Neuropilin 1(NRP-1) could inhibit breast cancer cell proliferation. Here, we continue exploring the roles and mechanisms of VEGF-A/NRP-1 axis in breast CSCs formation. Methods: qRT-PCR was used to detect the levels of VEGF-A and NRP-1 in breast cancer sphere cells and wild-type cells. Mammospheres formation, flow cytometry, soft agar colony and tumor formation assays were performed to evaluate the effects of VEGF-A/NRP-1 on breast cancer stemness. Further HUVECs tube formation, cell invasion assays were carried out to detect the effects of VEGF-A/NRP-1 on breast cancer spheres-induced angiogenesis. Finally, Annexin V/PI apoptosis and CCK8 assays were used to detect the effects of VEGF-A/NRP-1 on chemoresistance. Results: Overexpression of VEGF-A or NRP-1 conferred CSCs-related traits in MCF-7 cells, while knockdown of VEGF-A or NRP-1 reduced CSCs-related traits in MDA-MB-231 cells in vitro and in vivo. Notably, VEGF-A acted in a NRP-1 dependent way. Mechanistically, the VEGF-A/NRP-1 axis conferred CSCs phenotype via activating Wnt/β-catenin pathway. Conclusion: our results suggest that VEGF-A/NRP-1 axis could confer CSCs-related traits and chemoresistance.

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Section: Resultsmentioning

confidence: 99%

VEGF-A/Neuropilin 1 Pathway Confers Cancer Stemness via Activating Wnt/β-Catenin Axis in Breast Cancer Cells

Zhang

Wang

et al. 2017

Cell Physiol Biochem

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“…It is well established that ROS promotes EMT in mammary epithelial or breast cancer cells through diverse mechanisms [69, 70]. It is suggested that the activation of EGFR is involved in alcohol-promoted EMT [49] and alcohol may activate EGFR through intracellular ROS accumulation [66].…”

Section: Cellular and Molecular Mechanisms Underlying Alcohol-indumentioning

confidence: 99%

Cellular and molecular mechanisms underlying alcohol-induced aggressiveness of breast cancer

Wang

Zhang

et al. 2017

Pharmacological Research

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Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors. There are multiple potential mechanisms involved in alcohol-stimulated progression and aggressiveness of breast cancer. Alcohol may increase the mobility of cancer cells by inducing cytoskeleton reorganization and enhancing the cancer cell invasion by causing degradation and reconstruction of the extracellular matrix (ECM). Moreover, alcohol may promote the epithelial-mesenchymal transition (EMT), a hallmark of malignancy, and impair endothelial integrity, thereby increasing the dissemination of breast cancer cells and facilitating metastasis. Furthermore, alcohol may stimulate tumor angiogenesis through the activation of cytokines and chemokines which promotes tumor growth. Additionally, alcohol may increase the cancer stem cell population which affects neoplastic cell behavior, aggressiveness, and the therapeutic response. Alcohol can be metabolized in the mammary tissues and breast cancer cells which produces reactive oxygen species (ROS), causing oxidative stress. Recent studies suggest that the epidermal growth factor receptor (EGFR) family, particularly ErbB2 (a member of this family), is involved in alcohol-mediated tumor promotion. Breast cancer cells or mammary epithelial cells over-expressing ErbB2 are more sensitive to alcohol’s tumor promoting effects. There is considerable cross-talk between oxidative stress and EGFR/ErbB2 signaling. This review further discusses how the interaction between oxidative stress and EGFR/ErbB2 signaling contributes to the cellular and molecular events associated with breast cancer aggressiveness. We also discuss the potential therapeutic approaches for cancer patients who drink alcoholic beverages.

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“…FAM63B, LOC401464 and PARP3 autoantibodies could not be confirmed in the validation assays (Figure ), and hence, their relevance as immune targets in narcolepsy could not be verified. PARP3 is an enzyme with regulatory functions of processes including DNA damage responses and has been reported as a negative regulator of immunoglobulin class switch recombination . Protein expression is found in all major organs, including the brain .…”

Section: Discussionmentioning

confidence: 99%

Screening for autoantibody targets in post‐vaccination narcolepsy using proteome arrays

et al. 2020

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Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a specific loss of hypocretin‐producing neurons. The incidence of NT1 increased in Sweden, Finland and Norway following Pandemrix®‐vaccination, initiated to prevent the 2009 influenza pandemic. The pathogenesis of NT1 is poorly understood, and causal links to vaccination are yet to be clarified. The strong association with Human leukocyte antigen (HLA) DQB1*06:02 suggests an autoimmune pathogenesis, but proposed autoantigens remain controversial. We used a two‐step approach to identify autoantigens in patients that acquired NT1 after Pandemrix®‐vaccination. Using arrays of more than 9000 full‐length human proteins, we screened the sera of 10 patients and 24 healthy subjects for autoantibodies. Identified candidate antigens were expressed in vitro to enable validation studies with radiobinding assays (RBA). The validation cohort included NT1 patients (n = 39), their first‐degree relatives (FDR) (n = 66), population controls (n = 188), and disease controls representing multiple sclerosis (n = 100) and FDR to type 1 diabetes patients (n = 41). Reactivity towards previously suggested NT1 autoantigen candidates including Tribbles homolog 2, Prostaglandin D2 receptor, Hypocretin receptor 2 and α‐MSH/proopiomelanocortin was not replicated in the protein array screen. By comparing case to control signals, three novel candidate autoantigens were identified in the protein array screen; LOC401464, PARP3 and FAM63B. However, the RBA did not confirm elevated reactivity towards either of these proteins. In summary, three putative autoantigens in NT1 were identified by protein array screening. Autoantibodies against these candidates could not be verified with independent methods. Further studies are warranted to identify hypothetical autoantigens related to the pathogenesis of Pandemrix®‐induced NT1.

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PARP3 controls TGFβ and ROS driven epithelial-to-mesenchymal transition and stemness by stimulating a TG2-Snail-E-cadherin axis

Cited by 81 publications

References 55 publications

VEGF-A/Neuropilin 1 Pathway Confers Cancer Stemness via Activating Wnt/β-Catenin Axis in Breast Cancer Cells

VEGF-A/Neuropilin 1 Pathway Confers Cancer Stemness via Activating Wnt/β-Catenin Axis in Breast Cancer Cells

Cellular and molecular mechanisms underlying alcohol-induced aggressiveness of breast cancer

Screening for autoantibody targets in post‐vaccination narcolepsy using proteome arrays

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