Transforming Growth Factor-beta Regulation of Ephrin Type-A Receptor 4 Signaling in Breast Cancer Cellular Migration

Hachim, Ibrahim Y.; Villatoro, Manuel; Canaff, Lucie; Hachim, Mahmood Y.; Boudreault, Julien; Haiub, Halema; Ali, Suhad; Lebrun, Jean-Jacques

doi:10.1038/s41598-017-14549-9

Cited by 32 publications

(29 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the one hand, the loss of E-cadherin expression is associated with tumor development, metastatic dissemination, and poor patient prognosis (Oka et al., 1993, Schipper et al., 1991, Umbas et al., 1994). On the other hand, EphA4 is overexpressed in a wide range of cancers (including glioblastoma, pancreatic, colorectal, gastric, prostate, and breast cancers) and is often associated with poor patient prognosis and shorter survival (Ashida et al., 2004, Brantley-Sieders et al., 2011, Fukai et al., 2008, Hachim et al., 2017, Iiizumi et al., 2006, Lin et al., 2017, Miyazaki et al., 2013, Oki et al., 2008, Oshima et al., 2008). Moreover, it has been shown that high EphA4 expression negatively correlates with metastasis-free survival (Brantley-Sieders et al., 2011, Lin et al., 2017, Miyazaki et al., 2013, Oshima et al., 2008).…”

Section: Discussionmentioning

confidence: 99%

EphA4-ADAM10 Interplay Patterns the Cochlear Sensory Epithelium through Local Disruption of Adherens Junctions

et al. 2019

View full text Add to dashboard Cite

SummaryThe cochlear sensory epithelium contains a functionally important triangular fluid-filled space between adjacent pillar cells referred to as the tunnel of Corti. However, the molecular mechanisms leading to local cell-cell separation during development remain elusive. Here we show that EphA4 associates with ADAM10 to promote the destruction of E-cadherin-based adhesions between adjacent pillar cells. These cells fail to separate from each other, and E-cadherin abnormally persists at the pillar cell junction in EphA4 forward-signaling-deficient mice, as well as in the presence of ADAM10 inhibitor. Using immunolabeling and an in situ proximity ligation assay, we found that EphA4 forms a complex with E-cadherin and its sheddase ADAM10, which could be activated by ephrin-B2 across the pillar cell junction to trigger the cleavage of E-cadherin. Altogether, our findings provide a new molecular insight into the regulation of adherens junctions, which might be extended to a variety of physiological or pathological processes.

show abstract

Section: Discussionmentioning

confidence: 99%

EphA4-ADAM10 Interplay Patterns the Cochlear Sensory Epithelium through Local Disruption of Adherens Junctions

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Surgery, chemotherapy, endocrine therapy, and radiotherapy are still the main treatment methods for breast cancers. However, as breast cancers consist of a range of tumor subtypes with different clinical characteristics, the prognosis and treatment response of breast cancer patients is different [3]. Therefore, it is of great significance to find a novel, general and more efficient treatment therapy for breast cancers.…”

Section: Introductionmentioning

confidence: 99%

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

Wang

Lin

2020

IJMS

View full text Add to dashboard Cite

Breast cancer is a common malignancy threatening women's health around the world. Despite improved treatments for different subtypes of breast tumors that have been put forward, there still exists a poor therapeutic response and prognosis. Magnetic fields, as a non-invasive therapy, have shown anti-tumor effects in vitro and in vivo; however, the detailed mechanisms involved are still not clear. In this study, we found that in exposure to low-frequency magnetic fields (LF-MFs) with an intensity of 1 mT and frequencies of 50, 125, 200, and 275 Hz, separately, the proliferation of breast cancer cells was inhibited and LF-MF with 200 Hz reached the optimum inhibition effect, on exposure time-dependently. Notably, we found that exposure to LF-MF led to MCF-7 and ZR-75-1 cell apoptosis and cell cycle arrest. Moreover, we also discovered that LF-MF effectively increased the level of reactive oxygen species (ROS), suppressed the PI3K/AKT signaling pathway, and activated glycogen synthase kinase-3β (GSK-3β). We demonstrated that the GSK3β activity contributed to LF-MF-induced cell proliferation inhibition and apoptosis, while the underlying mechanism was associated with the inhibition of PI3K/AKT through increasing the intracellular ROS accumulation. These results indicate that LF-MF with a specific frequency may be an attractive therapy to treat breast cancers.Int. J. Mol. Sci. 2020, 21, 2952 2 of 14 processes [9]. Further research has found that low-frequency magnetic fields (LF-MFs), namely, those with a frequency below 300 Hz, possess a variety of effects such as the regulation of immunity [10] and inflammation [11], suppression of angiogenesis [12], contribution to differentiation [13], and induced apoptosis [14]. Although many biological effects of magnetic fields have been reported, the mechanisms involved still remain unclear.Reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are one of the main causes of tumors and play an important role in the process of tumor progression, metastasis and apoptosis [15]. Low-frequency magnetic fields have been demonstrated to significantly increase the intracellular ROS levels in many kinds of cells [16]. The PI3K/AKT pathway is a pivotal signaling pathway, which is closely related to the regulation of cell survival, apoptosis, migration and proliferation [17]. The relationship between ROS and the PI3K/AKT pathway in apoptosis regulation has been confirmed in several studies [18,19]. Glycogen synthase kinase-3β (GSK-3β) is an effector of PI3K/AKT, and is a kind of serine / threonine protein kinase, whose biological function is far beyond the glucose synthesis-regulating enzyme it was initially considered. GSK-3β can phosphorylate many substrates, including metabolism and signal protein, transcription factors of cell structural protein, etc., playing an important role in the process of tumor occurrence and development [20,21]. Baihuan Feng et al. reported that exposure to 50 Hz-0.4 mT MF affected mitochondrial permeability by the ROS-regulating phosphoryla...

show abstract

“…Precisely how the relationship between these two factors manifests clinically is still not known. Earlier studies using a panel of normal breast and breast cancer cases examined the expression of PRLR as well as TGFβRI and TGFβRII individually [16,23]. This study examined the pattern of co-expression of these receptors using the same clinical cases we used in our earlier studies in relation to various clinicopathological parameters.…”

Section: Resultsmentioning

confidence: 99%

Concomitant Expression of Prolactin Receptor and TGFβ Receptors in Breast Cancer: Association with Less Aggressive Phenotype and Favorable Patient Outcome

Hachim

López-Ozuna

Hachim

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

The epithelial–mesenchymal transition (EMT) process is known to play an essential role in tumor progression, metastasis and resistance to therapy. This report evaluated the prognostic value of co-expression of the receptor for prolactin (PRLR), a suppressor of EMT, and the receptors for transforming growth factor β (TGFβRI and TGFβRII), an inducer of EMT, in association with different clinicopathological parameters using TMA of 102 breast cancer patients and publicly available data on breast cancer patients. Interestingly, the results revealed that malignant tissues had significantly lower levels of concomitant protein expression of these receptors in comparison to normal/benign breast tissue. In addition, a higher level of concomitant expression was also observed in less aggressive breast cancer phenotypes, including low grade tumors, luminal breast cancer subtype, and less advanced stages of the disease (lymph node negative and early stages). Moreover, the results also showed that the expression of a gene signature composed of PRLR/TGFβRI/TGFβRII correlates more with differentiated grade I tumors, and identified a subset of patients showing better survival outcomes evident in luminal B and HER-2 enriched molecular subtypes. Together, these results indicate that loss of the co-expression of PRLR, TGFβRI and TGFβRII is indicative of aggressiveness and poor patient survival outcomes in breast cancer.

show abstract

Transforming Growth Factor-beta Regulation of Ephrin Type-A Receptor 4 Signaling in Breast Cancer Cellular Migration

Cited by 32 publications

References 62 publications

EphA4-ADAM10 Interplay Patterns the Cochlear Sensory Epithelium through Local Disruption of Adherens Junctions

EphA4-ADAM10 Interplay Patterns the Cochlear Sensory Epithelium through Local Disruption of Adherens Junctions

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

Concomitant Expression of Prolactin Receptor and TGFβ Receptors in Breast Cancer: Association with Less Aggressive Phenotype and Favorable Patient Outcome

Contact Info

Product

Resources

About