Targeting Signaling Pathways in Inflammatory Breast Cancer

Wang, Xiaoping; Semba, Takashi; Phi, Lan Thi; Chainitikun, Sudpreeda; Iwase, Toshiaki; Ueno, Naoto T.

doi:10.3390/cancers12092479

Cited by 27 publications

(27 citation statements)

References 112 publications

(168 reference statements)

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“…This is consistent with the upregulated levels of miR-181b-5p in IBC relative to stage-matched non-IBC. Given the hyperactivation of STAT3, NF-kB and upregulated IL-6 expression in IBC [ 54 ], we propose the same mechanism of regulation may be found in IBC. Remarkably, a significant upregulation of exosomal miR-181b than that free in plasma was proven in lung cancer patients, suggesting that sEV-derived miRNAs could efficiently mirror the expression pattern of carcinoma tissues [ 55 ].…”

Section: Discussionmentioning

confidence: 76%

Small extracellular vesicle-encapsulated miR-181b-5p, miR-222-3p and let-7a-5p: Next generation plasma biopsy-based diagnostic biomarkers for inflammatory breast cancer

et al. 2021

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Inflammatory breast cancer (IBC) is a rare, but aggressive entity of breast carcinoma with rapid dermal lymphatic invasion in young females. It is either poorly or misdiagnosed as mastitis because of the absence of a distinct lump. Small extracellular vesicles (sEVs) circulating in liquid biopsies are a novel class of minimally invasive diagnostic alternative to invasive tissue biopsies. They modulate cancer progression via shuttling their encapsulated cargo including microRNAs (miRNAs) into recipient cells to either trigger signaling or induce malignant transformation of targeted cells. Plasma sEVs < 200 nm were isolated using a modified cost-effective polyethylene glycol (PEG)-based precipitation method and compared to standard methods, namely ultracentrifugation and a commercial kit, where the successful isolation was verified by different approaches. We evaluated the expression levels of selected sEV-derived miR-181b-5p, miR-222-3p and let-7a-5p using quantitative real PCR (qPCR). Relative to non-IBC, our qPCR data showed that sEV-derived miR-181b-5p and miR-222-3p were significantly upregulated, whereas let-7a-5p was downregulated in IBC patients. Interestingly, receiver operating characteristic (ROC) curves analysis revealed that diagnostic accuracy of let-7a-5p alone was the highest for IBC with an area under curve (AUC) value of 0.9188, and when combined with miR-222-3p the AUC was improved to 0.973. Further, 38 hub genes were identified using bioinformatics analysis. Together, circulating sEV-derived miR-181b-5p, miR-222-3p and let-7a-5p serve as promising non-invasive diagnostic biomarkers for IBC.

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Section: Discussionmentioning

confidence: 76%

Small extracellular vesicle-encapsulated miR-181b-5p, miR-222-3p and let-7a-5p: Next generation plasma biopsy-based diagnostic biomarkers for inflammatory breast cancer

et al. 2021

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“…This may be due in part to 70% of IBC patients presenting with aggressive subtypes of HER2+ or triple-negative breast cancer (TNBC), compared with 40% of non-IBC tumors [ 8 ]. Efforts have been undertaken to identify molecular markers and therapeutic targets distinct to IBC and have identified important targets and pathways, including EGFR, E-cadherin, eIFG4I, RhoC, and TIG1/AXL [ 9 , 10 , 11 , 12 , 13 ]. However, no IBC-specific molecular signature or target has been identified thus far, and effective targeted therapies for this disease remain limited.…”

Section: Introductionmentioning

confidence: 99%

NDRG1 Expression Is an Independent Prognostic Factor in Inflammatory Breast Cancer

Villodre

Gong

et al. 2020

Cancers

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NDRG1 is widely described as a metastasis suppressor in breast cancer. However, we found that NDRG1 is critical in promoting tumorigenesis and brain metastasis in mouse models of inflammatory breast cancer (IBC), a rare but highly aggressive form of breast cancer. We hypothesized that NDRG1 is a prognostic marker associated with poor outcome in patients with IBC. NDRG1 levels in tissue microarrays from 64 IBC patients were evaluated by immunohistochemical staining with NDRG1 (32 NDRG1-low (≤median), 32 NDRG1-high (>median)). Overall and disease-free survival (OS and DSS) were analyzed with Kaplan–Meier curves and log-rank test. Univariate analysis showed NDRG1 expression, tumor grade, disease stage, estrogen receptor (ER) status, and receipt of adjuvant radiation to be associated with OS and DSS. NDRG1-high patients had poorer 10-year OS and DSS than NDRG1-low patients (OS, 19% vs. 45%, p = 0.0278; DSS, 22% vs. 52%, p = 0.0139). On multivariable analysis, NDRG1 independently predicted OS (hazard ratio (HR) = 2.034, p = 0.0274) and DSS (HR = 2.287, p = 0.0174). NDRG1-high ER-negative tumors had worse outcomes OS, p = 0.0003; DSS, p = 0.0003; and NDRG1-high tumors that received adjuvant radiation treatment had poor outcomes (OS, p = 0.0088; DSS, p = 0.0093). NDRG1 was a significant independent prognostic factor for OS and DSS in IBC patients. Targeting NDRG1 may represent a novel strategy for improving clinical outcomes for patients with IBC.

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“…Most tumors are often accompanied by abnormal activation or inhibition of various molecules and signaling pathways during their development and metastasis ( 22 , 23 ), and AMPK/mTOR signaling is one of the irreplaceable pathways in tumor cells ( 24 ) because it not only regulates the level of intracellular autophagy ( 25 ) but also regulates biological processes such as the proliferation, apoptosis and invasion of tumor cells ( 25 ). AMPK signaling plays a critical role in the development of almost all cancer cells, and its mechanism is to regulate tumor progression through a variety of downstream effector molecules or pathways, such as the mTOR complex ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

NRBP2 Functions as a Tumor Suppressor and Inhibits Epithelial-to-Mesenchymal Transition in Breast Cancer

Liu²,

et al. 2021

Front. Oncol.

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Nuclear Receptor Binding Protein 2 (NRBP2), one of the pseudokinases discovered during a screen of neural differentiation genes, inhibits tumor progression in medulloblastoma and hepatocellular carcinoma. However, the role and the mechanism of NRBP2 in the regulation of the progression of breast cancer (BC) have not been reported. In our study, NRBP2 was downregulated in human BC tissues compared with the corresponding normal tissues. Moreover, bioinformatics and cellular experiments illustrated that a lower level of NRBP2 contributed to a poor prognosis for patients with BC. In addition, we characterized the NRBP2-overexpressing BC cells and found that NRBP2 overexpression dramatically suppressed cell proliferation and invasion and inhibited the epithelial-mesenchymal transition (EMT) in cells in vitro, whereas knockdown of NRBP2 reversed these effects. Furthermore, overexpression of NRBP2 in the orthotopic breast tumor model significantly reduced lung metastatic nodules in nude mice. Mechanistically, NRBP2 regulated the activation of the 5′-adenosine monophosphate (AMP)-activated protein kinase/ mammalian target of rapamycin (AMPK/mTOR) signaling pathway. Moreover, the inhibition of cell proliferation, invasion and the EMT by NRBP2 overexpression was partially rescued after treatment with an AMPK inhibitor. Conversely, mTOR-specific inhibitors eliminated the effects of NRBP2 knockdown on increasing cell proliferation, invasion and the EMT, which suggested the anti-tumor effect of NRBP2, which may be partially related to the regulation of the AMPK/mTOR pathway. Taken together, NRBP2, a novel and effective prognostic indicator, inhibited the progression of BC and may become a potential therapeutic target for BC.

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Targeting Signaling Pathways in Inflammatory Breast Cancer

Cited by 27 publications

References 112 publications

Small extracellular vesicle-encapsulated miR-181b-5p, miR-222-3p and let-7a-5p: Next generation plasma biopsy-based diagnostic biomarkers for inflammatory breast cancer

Small extracellular vesicle-encapsulated miR-181b-5p, miR-222-3p and let-7a-5p: Next generation plasma biopsy-based diagnostic biomarkers for inflammatory breast cancer

NDRG1 Expression Is an Independent Prognostic Factor in Inflammatory Breast Cancer

NRBP2 Functions as a Tumor Suppressor and Inhibits Epithelial-to-Mesenchymal Transition in Breast Cancer

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