FYN promotes mesenchymal phenotypes of basal type breast cancer cells through STAT5/NOTCH2 signaling node

Lee, Ga Hang; Yoo, Kyoungkeun; An, Yoojeong; Lee, Hae June; Lee, Minyoung; Uddin, Nizam; Kim, Min Jung; Kim, In Gyu; Suh, Yongjoon; Lee, Su Jae

doi:10.1038/s41388-017-0114-y

Cited by 52 publications

(49 citation statements)

References 30 publications

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“…To investigate the interactive effects among genes of survival-related AS events, the top significant survival-associated genes in the OSCC cohort were uploaded to Cytoscape to generate an inter-gene interaction network. Several hub genes like PRKACA, CDC42, and FYN were identified (Figure 3b), which had previously been found to be associated with different cancers (Kastenhuber et al, 2017;Lee et al, 2018;Min et al, 2019).…”

Section: Identification Of Survival-associated As Events In Osccmentioning

confidence: 84%

Identification of a prognostic alternative splicing signature in oral squamous cell carcinoma

Zhang

Diao

et al. 2019

Journal Cellular Physiology

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Alternative splicing (AS) is critically associated with tumorigenesis and patient's prognosis.Here, we systematically analyzed survival-associated AS signatures in oral squamous cell carcinoma (OSCC) and evaluated their prognostic predictive values. Survival-related AS events were identified by univariate and multivariate Cox regression analyses using OSCC data from the TCGA head neck squamous cell carcinoma data set. The Percent Spliced In calculated by SpliceSeq from 0 to 1 was used to quantify seven types of AS events. A predictive model based on AS events was constructed by least absolute shrinkage and selection operator Cox regression assay and further validated using a training-testing cohort design. Patient survival was estimated using the Kaplan-Meier method and compared with Log-rank test. The receiver operating characteristics curve area under the curves was used to evaluate the predictive abilities of these predictive models.Furthermore, gene-gene interaction networks and the splicing factors (SFs)-AS regulatory network was generated by Cytoscape. A total of 825 survival-related AS events within 719 genes were identified in OSCC samples. The integrative predictive model was better at predicting outcomes of patients as compared to those models built with the individual AS event. The predictive model based on three AS-related genes also effectively predicted patients' survival. Moreover, seven survival-related SFs were detected in OSCC including RBM4, HNRNPD, and HNRNPC, which have been linked to tumorigenesis. The SF-AS network revealed a significant correlation between survival-related AS genes and these SFs. Our findings revealed a systemic portrait of survival-associated AS events and the splicing network in OSCC, suggesting that AS events might serve as novel prognostic biomarkers and therapeutic targets for OSCC. K E Y W O R D Salternative splicing, oral squamous cell carcinoma, prognosis, splicing factor

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Section: Identification Of Survival-associated As Events In Osccmentioning

confidence: 84%

Identification of a prognostic alternative splicing signature in oral squamous cell carcinoma

Zhang

Diao

et al. 2019

Journal Cellular Physiology

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“…The Notch pathway cooperates in the initiation and progression of breast cancer metastasis. Lee et al [8] found that the protein kinase Fyn plays a significant role in promoting breast cancer tumorigenicity via the Notch2 signaling pathway. Hu et al [9] found that the application of Brucine could inhibit Notch1 pathway and thereby reduce bone metastasis of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Linc00514 promotes breast cancer metastasis and M2 polarization of tumor-associated macrophages via Jagged1-mediated notch signaling pathway

Tao

Chen

et al. 2020

J Exp Clin Cancer Res

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Background Tumor-associated macrophages (TAMs) and tumor cells are important components of the tumor microenvironment. M2 polarization of TAMs, which is a major actor in breast cancer malignancy and metastasis, can be induced by breast cancer cells. However, the potential mechanisms of the interaction between breast cancer cells and TAMs remain unclear. Methods The candidate breast cancer-associated long non-coding RNAs (lncRNAs) were analyzed using the GEO database. Functional assays, including MTT assay, Transwell assay, and EdU labeling detection, were performed to investigate the oncogenic role of linc00514 in breast cancer progression. The co-culture and ELISA assays were used to assess the role of linc00514 in macrophage recruitment and M2 polarization. RNA immunoprecipitation, RNA pull-down, and luciferase reporter assays were applied to determine the mechanism of linc00514 in breast cancer metastasis. Mouse xenograft models, mouse pulmonary metastatic models, and mouse primary tumor models were used to assess the role of linc00514 in M2 macrophage polarization and breast cancer tumorigenicity. Results Linc00514 was highly expressed in clinical breast cancer tissues and breast cancer cell lines. Overexpression of linc00514 promoted the proliferation and invasion of breast cancer cells and increased xenograft tumor volumes and pulmonary metastatic nodules. Overexpression of linc00514 also increased the percentage of macrophages expressing M2 markers CD206 and CD163. Mechanistically, linc00514 promoted Jagged1 expression in a transcriptional manner by increasing the phosphorylation of a transcription factor STAT3. Subsequently, Jagged1-mediated Notch signaling pathway promoted IL-4 and IL-6 secretions in breast cancer cells and ultimately inducing M2 polarization of macrophages. Conclusion Linc00514 plays an important role in regulating breast cancer tumorigenicity and M2 macrophage polarization via Jagged1-mediated Notch signaling pathway.

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“…In addition, Karsan and colleagues showed that Slug is a direct target gene of Notch1 in breast cancer (Leong et al, 2007). In line with these findings, Suh and colleagues demonstrated that Notch2 up-regulates multiple EMT-associated markers including Twist, Snail1, Slug, Vimentin, and Zeb1 in basal type breast cancer cells (Lee et al, 2018). Clinical studies performed in breast cancer patients demonstrate that Notch signaling activation is associated with reduced overall survival and poor prognosis (Reedijk et al, 2005;Dickson et al, 2007), underscoring the importance of this signaling pathway for tumor progression in human breast cancer.…”

Section: Notch Pathwaymentioning

confidence: 80%

Cellular Plasticity in Breast Cancer Progression and Therapy

Kong

Hughes

Ford

2020

Front. Mol. Biosci.

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With the exception of non-melanoma skin cancer, breast cancer is the most frequently diagnosed malignant disease among women, with the majority of mortality being attributable to metastatic disease. Thus, even with improved early screening and more targeted treatments which may enable better detection and control of early disease progression, metastatic disease remains a significant problem. While targeted therapies exist for breast cancer patients with particular subtypes of the disease (Her2+ and ER/PR+), even in these subtypes the therapies are often not efficacious once the patient's tumor metastasizes. Increases in stemness or epithelial-to-mesenchymal transition (EMT) in primary breast cancer cells lead to enhanced plasticity, enabling tumor progression, therapeutic resistance, and distant metastatic spread. Numerous signaling pathways, including MAPK, PI3K, STAT3, Wnt, Hedgehog, and Notch, amongst others, play a critical role in maintaining cell plasticity in breast cancer. Understanding the cellular and molecular mechanisms that regulate breast cancer cell plasticity is essential for understanding the biology of breast cancer progression and for developing novel and more effective therapeutic strategies for targeting metastatic disease. In this review we summarize relevant literature on mechanisms associated with breast cancer plasticity, tumor progression, and drug resistance.

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FYN promotes mesenchymal phenotypes of basal type breast cancer cells through STAT5/NOTCH2 signaling node

Cited by 52 publications

References 30 publications

Identification of a prognostic alternative splicing signature in oral squamous cell carcinoma

Identification of a prognostic alternative splicing signature in oral squamous cell carcinoma

Linc00514 promotes breast cancer metastasis and M2 polarization of tumor-associated macrophages via Jagged1-mediated notch signaling pathway

Cellular Plasticity in Breast Cancer Progression and Therapy

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