The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer

Forte, Luca; Turdo, Federica; Ghirelli, Cristina; Aiello, Piera; Casalini, Patrizia; Iorio, Marilena V.; D’Ippolito, Elvira; Gasparini, Patrizia; Agresti, Roberto; Belmonte, Beatrice; Sozzi, Gabriella; Sfondrini, Lucia; Tagliabue, Elda; Campiglio, Manuela; Bianchi, Francesca

doi:10.1186/s12885-018-4500-9

Cited by 21 publications

(16 citation statements)

References 39 publications

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“…For instance, TNBC patients frequently harbour higher expression of EGFR; however, studies have failed to establish significant benefit from EGFRtargeted therapies or tyrosine kinase inhibitors, suggesting the need to therapeutically target other pathways in these tumors 38,39 . Moreover, the significance and over-activation of pathways such as; P38 MAPK , the PDGF, and the RAS pathways in BC metastatic sites and their association with DMFS and BCSS in TNBC have been previously documented [40][41][42] .…”

Section: Discussionmentioning

confidence: 99%

A novel prognostic two-gene signature for triple negative breast cancer

et al. 2020

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Background: The absence of a robust risk stratification tool for triple negative breast cancer (TNBC) underlies imprecise and non-selective treatment of these patients with cytotoxic chemotherapy. This study aimed to interrogate transcriptomes of TNBC resected samples using next generation sequencing (NGS) to identify novel biomarkers associated with disease outcomes. Methods: A subset of cases (n=112) from a large, diverse and well-characterised cohort of primary TNBCs (n=333) were subjected to RNA-sequencing (60M total reads/sample) and analyzed using the Illumina HiSeq 2500 platform. We identified genes associated with distant metastasis-free survival (DMFS) and breast cancer-specific survival (BCSS) by combining the application of supervised artificial neuronal network (ANN) analysis with gene selection to the RNA-sequencing data. The prognostic ability of these genes was validated using the Breast Cancer Gene-Expression Miner v4. 0 and Genotype 2 outcome datasets. Multivariate Cox regression analysis identified a prognostic gene signature that was independently associated with poor prognosis. Finally, we corroborated our results from the two-gene prognostic signature by their protein expression using immunohistochemistry. Results: ANN identified two gene panels that strongly predicted DMFS and BCSS. Univariate Cox regression analysis of 21 genes common to both panels revealed that the expression level of eight genes was independently associated with poor prognosis (p<0.05). Adjusting for clinicopathological factors including patient's age, grade, nodal stage, tumor size, and lymphovascular invasion using multivariate Cox regression analysis yielded a two-gene prognostic signature (ACSM4 and SPDYC) which was associated with poor prognosis (p<0.05) independent of other prognostic variables. We validated the protein expression of these two genes, and it was significantly associated with patient outcome in both independent and combined manner (p<0.05). Conclusion: Our study identifies a prognostic gene signature that can predict prognosis in TNBC patients and could potentially be used to guide the clinical management of TNBC patients.

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Section: Discussionmentioning

confidence: 99%

A novel prognostic two-gene signature for triple negative breast cancer

et al. 2020

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“…Moreover, ERK1/2 is a well‐known kinase that can be phosphorylated by many cytokines. It is closely related to tumour growth and metastasis . The activation of ERK promotes proliferation and metastasis of gallbladder cancer cells .…”

Section: Introductionmentioning

confidence: 99%

Homeobox B5 suppression attenuates proliferation and elevates apoptosis in hepatoma cell lines through ERK/MDM2 signalling

Zhang

Luo

2020

Clin Exp Pharma Physio

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Homeobox B5 (HOXB5), a member of the HOX gene family, is an important gene in tumourigenesis. However, its role in hepatocellular carcinoma (HCC) cell proliferation and apoptosis remains unclear. In this study, we investigated the role and regulation mechanism of HOXB5 in HCC cell lines Hep3B and LM6. The data indicated high expression of HOXB5 in HCC tissues and cell lines. In HCC cells, inhibition of HOXB5 by transfection with HOXB5 siRNA significantly constrained cell viability, and Bcl‐2 levels, and it increased cell apoptosis, cytochrome c levels, BAX levels, and caspase‐3 activity. On the contrary, HOXB5 overexpression increased proliferation and Bcl‐2 levels but inhibited BAX levels and caspase‐3 activity in these cells. HOXB5 downregulation attenuated activation of extracellular signal‐regulated kinase (ERK) and expression of the murine double minute 2 (MDM2) oncogene. Incubation with the ERK activator, phorbol 12‐myristate 13‐acetate (40 μmol/L), for 12 hours reversed the effects of HOXB5 inhibition on MDM2 expression, cell proliferation, and apoptosis in HCC cells. Overall, this study demonstrated that HOXB5 inhibition regulated MDM2 expression by controlling ERK activation and that it modulated proliferation and apoptosis in HCC cells.

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“…Accordingly, we have established that growth factors that are released during wound healing following surgery account for the early relapse of the HER2-positive breast cancer subtype [17,18]. Moreover, we recently demonstrated that exposure of triple-negative (TN) breast cancer cells to WHF in vitro increases their expression of CDCP1, a molecule that is associated with a poor prognosis in several types of tumor, including TNBC [19,20].…”

Section: Introductionmentioning

confidence: 99%

Wound Healing Fluid Reflects the Inflammatory Nature and Aggressiveness of Breast Tumors

Agresti

Triulzi

Sasso

et al. 2019

Cells

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Wound healing fluid that originates from breast surgery increases the aggressiveness of cancer cells that remain after the surgery. We determined the effects of the extent of surgery and tumor-driven remodeling of the surrounding microenvironment on the ability of wound-healing to promote breast cancer progression. In our analysis of a panel of 34 cytokines, chemokines, and growth factors in wound healing fluid, obtained from 27 breast carcinoma patients after surgery, the levels of several small molecules were associated with the extent of cellular damage that was induced by surgery. In addition, the composition of the resulting wound healing fluid was associated with molecular features of the removed tumor. Specifically, IP-10, IL-6, G-CSF, osteopontin, MIP-1a, MIP-1b, and MCP1-MCAF were higher in more aggressive tumors. Altogether, our findings indicate that the release of factors that are induced by removal of the primary tumor and subsequent wound healing is influenced by the extent of damage due to surgery and the reactive stroma that is derived from the continuously evolving network of interactions between neoplastic cells and the microenvironment, based on the molecular characteristics of breast carcinoma cells.

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The PDGFRβ/ERK1/2 pathway regulates CDCP1 expression in triple-negative breast cancer

Cited by 21 publications

References 39 publications

A novel prognostic two-gene signature for triple negative breast cancer

A novel prognostic two-gene signature for triple negative breast cancer

Homeobox B5 suppression attenuates proliferation and elevates apoptosis in hepatoma cell lines through ERK/MDM2 signalling

Wound Healing Fluid Reflects the Inflammatory Nature and Aggressiveness of Breast Tumors

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