Epiregulin contributes to breast tumorigenesis through regulating matrix metalloproteinase 1 and promoting cell survival

Farooqui, Mariya; Bohrer, Laura R.; Brady, Nicholas J.; Chuntova, Pavlina; Kemp, Sarah E.; Wardwell, C. Taylor; Nelson, Andrew C.; Schwertfeger, Kathryn L.

doi:10.1186/s12943-015-0408-z

Cited by 30 publications

(30 citation statements)

References 39 publications

(51 reference statements)

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“…MMPs are involved in breakdown of the extracellular matrix, tissue healing, and remodeling (Martins et al 2013; Nagase and Woessner 1999). In this study, MMP1 was the most up-regulated gene, and examination of EREG-induced signaling pathways has demonstrated that EREG promotes cell survival through regulating the expression of MMP1 (Boström et al 2011; Farooqui et al 2015). Our results also suggest that MMP1 has a strong ability to promote cancer invasion and metastasis.…”

Section: Discussionmentioning

confidence: 85%

The effects for PM2.5 exposure on non-small-cell lung cancer induced motility and proliferation

et al. 2016

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BackgroundIncreasing urbanization and associated air pollution, including elevated levels of particulate matter (PM), are strongly correlated with the development of various respiratory diseases. In particular, PM2.5 has been implicated in promoting lung cancer initiation, growth and progression. Cell migration and proliferation are crucial for the progression of cancer. However, the molecular signatures and biological networks representing the distinct and shared features of non-small cell lung cancer (NSCLC) after PM2.5 exposure are unknown.ResultsFunctional assays demonstrated higher proliferation, migration and invasion of cancer cells stimulated with PM2.5. To investigate the complicated mechanisms, we performed global transcriptome profiling of the A549 cell line. Particularly, transcriptome sequencing revealed invasive characteristics reminiscent of cancer cells. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining the invasive and proliferative properties of PM2.5-exposed cells, respectively. Interestingly, under the PM2.5-stimulated condition, the A549 and H1299 cells strengthened obviously properties in motility and proliferation. Based on the network model reconstructing the shared protein–protein interactions, we selected the two most up-regulated genes, interleukin-1β (IL1β) and matrix metalloprotease 1 (MMP1), as key regulators responsible for the effects of PM2.5 exposure. Notably, IL1β and MMP1 expression was elevated in independent assays, which was further enhanced by PM2.5.ConclusionTaken together, our systems approach to investigating PM2.5 exposure provides a basis to identify key regulators responsible for the pathological features of NSCLC.

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Section: Discussionmentioning

confidence: 85%

The effects for PM2.5 exposure on non-small-cell lung cancer induced motility and proliferation

et al. 2016

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“…In the cytoplasm, lncRNAs regulate gene expression mainly at post-transcriptional level. On the one hand, lncRNAs can facilitate mRNA decay, stabilize mRNAs, and promote or inhibit the translation of target mRNAs through extended base-pairing [ 20 ]. On the other hand, lncRNAs can also function as the microRNAs precursor or compete for microRNA-mediated inhibition, as is the case for the competing endogenous RNAs (ceRNA) [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

LINC00885 a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression

Abba

Canzoneri

Gurruchaga

et al. 2020

IJMS

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Long intergenic non-protein coding RNA 885 (LINC00885) was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by LINC00885 in non-invasive and invasive breast cancer models. We determined that LINC00885 induces premalignant phenotypic changes by increasing cell proliferation, motility, migration and altering 3D growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by LINC00885, which include bioprocesses related to TP53 signaling pathway and proliferative signatures such as activation of EREG, EGFR and FOXM1 pathways. LINC00885 silencing in breast cancer lines overexpressing this lncRNA leads to downregulation of proliferation related transcripts such as EREG, CMYC, CCND1 and to significant decrease in cell migration and motility. TCGA-BRCA data analyses show an association between high LINC00885 expression and worse overall survival in patients with primary invasive breast carcinomas (p = 0.024), suggesting that the pro-tumorigenic effects of LINC00885 overexpression persist post-invasion. We conclude that LINC00885 behaves as a positive regulator of cell growth both in normal and DCIS breast cells possibly operating as a ceRNA and representing a novel oncogenic lncRNA associated with early stage breast cancer progression.

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“…We further demonstrated that CUZD1 is recruited along with pSTAT5 to the regulatory regions of key target genes, such as Ereg and Wap . It is plausible that EREG contributes to CUZD1-mediated epithelial proliferation and alveolar expansion during pregnancy and lactation, as Ereg is a direct transcriptional target of STAT5 and has been implicated in promoting growth and survival of breast cancer cells [40–42]. …”

Section: Discussionmentioning

confidence: 99%

CUZD1 is a critical mediator of the JAK/STAT5 signaling pathway that controls mammary gland development during pregnancy

Mapes

Kannan

et al. 2017

PLoS Genet

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In the mammary gland, genetic circuits controlled by estrogen, progesterone, and prolactin, act in concert with pathways regulated by members of the epidermal growth factor family to orchestrate growth and morphogenesis during puberty, pregnancy and lactation. However, the precise mechanisms underlying the crosstalk between the hormonal and growth factor pathways remain poorly understood. We have identified the CUB and zona pellucida-like domain-containing protein 1 (CUZD1), expressed in mammary ductal and alveolar epithelium, as a novel mediator of mammary gland proliferation and differentiation during pregnancy and lactation. Cuzd1-null mice exhibited a striking impairment in mammary ductal branching and alveolar development during pregnancy, resulting in a subsequent defect in lactation. Gene expression profiling of mammary epithelium revealed that CUZD1 regulates the expression of a subset of the EGF family growth factors, epiregulin, neuregulin-1, and epigen, which act in an autocrine fashion to activate ErbB1 and ErbB4 receptors. Proteomic studies further revealed that CUZD1 interacts with a complex containing JAK1/JAK2 and STAT5, downstream transducers of prolactin signaling in the mammary gland. In the absence of CUZD1, STAT5 phosphorylation in the mammary epithelium during alveologenesis was abolished. Conversely, elevated expression of Cuzd1 in mammary epithelial cells stimulated prolactin-induced phosphorylation and nuclear translocation of STAT5. Chromatin immunoprecipitation confirmed co-occupancy of phosphorylated STAT5 and CUZD1 in the regulatory regions of epiregulin, a potential regulator of epithelial proliferation, and whey acidic protein, a marker of epithelial differentiation. Collectively, these findings suggest that CUZD1 plays a critical role in prolactin-induced JAK/STAT5 signaling that controls the expression of key STAT5 target genes involved in mammary epithelial proliferation and differentiation during alveolar development.

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Epiregulin contributes to breast tumorigenesis through regulating matrix metalloproteinase 1 and promoting cell survival

Cited by 30 publications

References 39 publications

The effects for PM2.5 exposure on non-small-cell lung cancer induced motility and proliferation

The effects for PM2.5 exposure on non-small-cell lung cancer induced motility and proliferation

LINC00885 a Novel Oncogenic Long Non-Coding RNA Associated with Early Stage Breast Cancer Progression

CUZD1 is a critical mediator of the JAK/STAT5 signaling pathway that controls mammary gland development during pregnancy

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