Coordinated Expression of Pax-5 and FAK1 in Metastasis

Crapoulet, Nicolas; O'Brien, Pierre; Ouellette, Rodney J.; Robichaud, Gilles A.

doi:10.2174/187152011796817637

Cited by 14 publications

(19 citation statements)

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“…Intriguingly, Pax-5 seems to confer an anti-proliferative effect in most carcinomas studied in contrast to its stimulatory effect on B cell proliferation 21, 34. Most importantly, we and others show that Pax-5 expression reduces mesenchymal marker expression, colony formation and migratory capabilities while concomitantly inducing epithelial characteristics in invasive breast carcinoma cells 21, 22, 35.…”

Section: Introductionmentioning

confidence: 51%

“…However, we have previously reported that the expression profiles of pro-epithelial factor Pax-5 inversely correlate with those from pro-malignant FAK 22. We therefore set out to establish and elucidate a possible regulatory mechanism between the Pax-5 transcription factor and FAK in breast cancer processes.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we and others have reported roles for the Pax-5 transcription factor in breast cancer epithelial features that are reminiscent of MET 21, 22. Pax-5 is a member of the Paired Box (PAX) gene family which control gene expression programs pivotal in cellular processes such as proliferation, differentiation and apoptosis 23-25.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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The study of genetic factors regulating breast cancer malignancy is a top priority to mitigate the morbidity and mortality associated with this disease. One of these factors, Pax-5, modulates cancer aggressiveness through the regulation of various components of the epithelial to mesenchymal transitioning (EMT) process. We have previously reported that Pax-5 expression profiles in cancer tissues inversely correlate with those of the Focal Adhesion Kinase (FAK), a potent activator of breast cancer malignancy. In this study, we set out to elucidate the molecular and regulatory relationship between Pax-5 and FAK in breast cancer processes. Interestingly, we found that Pax-5 mediated suppression of breast cancer cell migration is dependent of FAK activity. Our mechanistic examination revealed that Pax-5 inhibits FAK expression and activation. We also demonstrate that Pax-5 is a potent modulator of FAK repressors (p53 and miR-135b) and activator (NFκB) which results in the overall suppression of FAK-mediated signaling cascades. Altogether, our findings bring more insight to the molecular triggers regulating phenotypic transitioning process and signaling cascades leading to breast cancer progression.

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Section: Introductionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…In most cases, Pax-5 expression correlates with increasing disease malignancy. Furthermore, recent findings have shown that Pax-5 expression is present in breast cancer (18,19) and is thought to be involved in metastatic progression (20). Taken together, these results add to the growing body of evidence that implicates Pax-5 activity in diverse nonhematopoietic solid tumor malignancies.…”

Section: Pax-5 Expression In Nonhematopoietic Cancersmentioning

confidence: 58%

“…Of interest, a gene expression microarray analysis revealed a 100-fold overexpression of Pax-5 in breast cancer cells that metastasized to lymph nodes compared with the primary tumor (27). Moreover, Pax-5 has been shown to suppress the expression of the proinvasive focal adhesion kinase, reminiscent of the mesenchymal-epithelial transition (20). Collectively, these findings suggest the involvement of Pax-5 in breast cancer and its progression to metastasis.…”

Section: Dichotomous Roles Of Pax-5 In Metastasismentioning

confidence: 96%

The Pax-5 Gene: A Pluripotent Regulator of B-cell Differentiation and Cancer Disease

et al. 2011

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The Pax-5 oncogene encodes a potent transcription factor that plays a key role in B-cell development and cancerous processes. In normal B-lymphopoiesis, Pax-5 accomplishes a dual function by activating B-cell commitment genes while concomitantly repressing non-B-lineage genes. Given the pivotal importance of Pax-5-mediated processes in B-cell development, an aberrant regulation of Pax5 expression has consistently been associated with B-cell cancers, namely, lymphoma and lymphocytic leukemias. More recently, Pax-5 gene expression has been proposed to influence carcinogenic events in tissues of nonlymphoid origin by promoting cell growth and survival. However, in other cases, Pax-5 products have opposing effects on proliferative activity, thus redefining its generally accepted role as an oncogene in cancer. In this review, we attempt to summarize recent findings about the function and regulation of Pax-5 gene products in B-cell development and related cancers. In addition, we present new findings that highlight the pleiotropic effects of Pax-5 activity in a number of other cancer types. Cancer Res; 71(24); 7345-50. Ó2011 AACR.

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Pax-5 Inhibits NF-κB Activity in Breast Cancer Cells Through IKKε and miRNA-155 Effectors

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LeBlanc

Landry

et al. 2018

J Mammary Gland Biol Neoplasia

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Pax-5, an essential transcription factor in B cell development, is aberrantly expressed in various B cell cancer lesions and solid tumors such as breast carcinoma. We have recently shown that Pax-5 regulates NF-κB activity which lead to the modulation of breast cancer phenotypic features (EMT-MET). NF-κB is known as a central mediator in inflammation, stress response as well as being a gatekeeper of pro-tumorigenic activity. However, little is known as to how Pax-5 affects this modulation. We thus turned our attention to microRNAs as potential regulatory effectors. In this study, we set out to elucidate the regulatory network between differential Pax-5 expression and NF-κB activity which dictate breast cancer malignancy. Through next-generation sequencing (NGS) of breast cancer cells conditionally expressing Pax-5, we profile significantly upregulated microRNAs; including microRNA-155, a known regulator of pathological processes and suppressor of malignant growth. Through the conditional expression of microRNA-155 in breast cancer models, we identify and validate IKKε (IKBKE) as a downstream target and an essential effector of Pax-5-mediated suppression of NF-κB signaling. Using rescue experiments, we also confirm that Pax-5 modulates NF-κB activity via IKKε downregulation. Interestingly, we also show that microRNA-155, in turn, supresses Pax-5 expression, indicative of an auto-regulatory feedback loop. Altogether, we demonstrate that Pax-5 inhibits NF-κB signalling through the regulation of microRNA-155 and its downstream target IKKε. The elucidation of this signaling network is relevant as Pax-5 and NF-κB are potent transcriptional regulators of breast cancer aggressivity. In addition, IKKε is relevant oncogene aberrantly expressed in 30% of breast carcinomas. Further insight into the regulatory pathways of breast cancer progression will eventually identify strategic therapeutic and prognostic targets to improve cancer patient outcome.

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Coordinated Expression of Pax-5 and FAK1 in Metastasis

Cited by 14 publications

References 0 publications

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

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

The Pax-5 Gene: A Pluripotent Regulator of B-cell Differentiation and Cancer Disease

Pax-5 Inhibits NF-κB Activity in Breast Cancer Cells Through IKKε and miRNA-155 Effectors

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