Breast Cancer Malignant Processes are Regulated by Pax-5 Through the Disruption of FAK Signaling Pathways

Benzina, Sami; Harquail, Jason; Guerrette, Roxann; O'Brien, Pierre; Jean, Stéphanie; Crapoulet, Nicolas; Robichaud, Gilles A.

doi:10.7150/jca.15200

Cited by 17 publications

(12 citation statements)

References 63 publications

(73 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, miR-135b-5p has been well documented as a tumor suppressor [33][34][35] or oncogene [36][37][38] in breast cancer, but less is known about the expression and function of miR-135b-3p. In case that both 5p and 3p strands are functional and not degraded, despite targeting different mRNAs, they might cooperate temporally and result in a synergistic effect.…”

Section: Discussionmentioning

confidence: 99%

Exploring specific prognostic biomarkers in triple-negative breast cancer

Bao

Chen

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

Lacking of both prognostic biomarkers and therapeutic targets, triple-negative breast cancer (TNBC) underscores pivotal needs to uncover novel biomarkers and viable therapies. MicroRNAs have broad biological functions in cancers and may serve as ideal biomarkers. In this study, by data mining of the Cancer Genome Atlas database, we screened out 4 differentially-expressed microRNAs (DEmiRNAs) between TNBC and normal samples: miR-135b-5p, miR-9-3p, miR-135b-3p and miR-455-5p. They were specially correlated with the prognosis of TNBC but not non-TNBC. The weighted correlation network analysis (WGCNA) for potential target genes of 3 good prognosis-related DEmiRNAs (miR-135b-5p, miR-9-3p, miR-135b-3p) identified 4 hub genes with highly positive correlation with TNBC subtype: FOXC1, BCL11A, FAM171A1 and RGMA. The targeting relationships between miR-9-3p and FOXC1/FAM171A1, miR-135b-3p and RGMA were validated by dual-luciferase reporter assays. Importantly, the regulatory functions of 4 DEmiRNAs and 3 verified target genes on cell proliferation and migration were explored in TNBC cell lines. In conclusion, we shed lights on these 4 DEmiRNAs (miR-135b-5p, miR-9-3p, miR-135b-3p, miR-455-5p) and 3 hub genes (FOXC1, FAM171A1, RGMA) as specific prognostic biomarkers and promising therapeutic targets for TNBC.

show abstract

Section: Discussionmentioning

confidence: 99%

Exploring specific prognostic biomarkers in triple-negative breast cancer

Bao

Chen

et al. 2019

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…However, the function of PLK4 in NB tumorigenesis and metastasis remains to be elucidated. The transformation of a cell with epithelial characteristics into one with mesenchymal traits occurs during the epithelial–mesenchymal transition (EMT) process, which has been uncovered to play a significant role in tumor development 25 , and the activation of EMT is commonly reflected a vested feature of malignancy 26 , 27 . EMT was also reported to be associated with the migratory and invasive properties of human NB cells 28 .…”

Section: Introductionmentioning

confidence: 99%

Polo-like kinase 4 mediates epithelial–mesenchymal transition in neuroblastoma via PI3K/Akt signaling pathway

et al. 2018

View full text Add to dashboard Cite

Neuroblastoma (NB) is the most common malignant tumor in infancy and most common extracranial solid tumor in childhood. With the improvement of diagnosis and treatment, the survival rate of patients with low-risk and intermediate-risk NB can reach up to 90%. In contrast, for high-risk NBs, the long-term survival rate is still <40% because of heterogeneity of this tumor. The pathogenesis of NB is still not explicit, therefore it is of great significance to explore the mechanism of NB tumorigenesis and discover new therapeutic targets for NB. Polo-like kinase 4 (PLK4), one of the polo-like kinase family members, is an important regulator of centriole replication. The aberrant expression of PLK4 was found in several cancers and a recent study has unraveled a novel function of PLK4 as a mediator of invasion and metastasis in Hela and U2OS cells. However, the function of PLK4 in NB development and progression remains to be elucidated. The study showed the expression level of PLK4 in NB tissues was remarkably upregulated and high expression of PLK4 was negatively correlated with clinical features and survival, which suggested that PLK4 could be a potential tumor-promoting factor of NB. Functional studies indicated downregulation of PLK4 suppressed migration and invasion and promoted apoptosis in NB cells. Further experiments showed that downregulation of PLK4 in NB cells inhibited EMT through the PI3K/Akt signaling pathway. Animal experiments demonstrated that the downregulation of PLK4 in SK-N-BE(2) cells dramatically suppressed tumorigenesis and metastasis. PLK4 may be a promising therapeutic target for NB.

show abstract

“…Furthermore, 9 downregulated and 2 upregulated genes were selected for validation using qRT-PCR, and they were all consistent with the findings of RNA-seq. Interestingly, we found that COMP, ITGA11, COL4A6, RAC2, and CCND2 were associated with the FAK signaling pathway 18 - 20 , which plays a fundamental role in cancer progression and metastasis 21 , 22 . The focal adhesion proteins such as FAK, regulate cell spreading, adhesion, migration, proliferation and angiogenesis, and FAK expression correlates with tumor invasion, metastatic potential and poor disease outcome 23 .…”

Section: Discussionmentioning

confidence: 92%

CPNE3 promotes migration and invasion in non-small cell lung cancer by interacting with RACK1 via FAK signaling activation

et al. 2018

View full text Add to dashboard Cite

Approximately 90% of patients diagnosed with non-small cell lung cancer (NSCLC) die due to distant metastases. However, the complicated molecular and cellular mechanisms involved in lung cancer metastasis remain poorly understood. Copine III (CPNE3), a member of a Ca2+-dependent phospholipid-binding protein family, was identified as a novel metastasis-associated protein in NSCLC in our previous study, however, its function in metastasis remains unclear. Here, we found that CPNE3 was expressed at high levels in NSCLC tissues and advanced TNM stages and was significantly associated with poor prognosis. In addition, CPNE3 interacted with phosphorylated erb-b2 receptor tyrosine kinase 2 (pErbB2) and receptor of activated protein C kinase 1 (RACK1) and activated the focal adhesion (FA) signaling pathway in NSCLC cells. Moreover, knockdown of RACK1 inhibited cell motility in the CPNE3-overexpressed NSCLC cells. These findings offer mechanistic insights into the oncogenic roles of CPNE3 and the pivotal effects of CPNE3 as a biomarker and therapeutic target for NSCLC metastasis.

show abstract

Breast Cancer Malignant Processes are Regulated by Pax-5 Through the Disruption of FAK Signaling Pathways

Cited by 17 publications

References 63 publications

Exploring specific prognostic biomarkers in triple-negative breast cancer

Exploring specific prognostic biomarkers in triple-negative breast cancer

Polo-like kinase 4 mediates epithelial–mesenchymal transition in neuroblastoma via PI3K/Akt signaling pathway

CPNE3 promotes migration and invasion in non-small cell lung cancer by interacting with RACK1 via FAK signaling activation

Contact Info

Product

Resources

About