Epithelial Paradox: Clinical Significance of Coexpression of E-cadherin and Vimentin With Regard to Invasion and Metastasis of Breast Cancer

Yamashita, Nami; Tokunaga, Eriko; Iimori, Makoto; Inoue, Yuichi; Tanaka, Kimihiro; Kitao, Hiroyuki; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko

doi:10.1016/j.clbc.2018.02.002

Cited by 70 publications

(61 citation statements)

References 33 publications

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“…First, we individually assessed the prognostic performance of CTC‐specific miR‐106b, E‐cadherin, and vimentin by plotting the ROC curve in 128 patients. Consistent with other studies , in our study, CTC‐specific E‐cadherin and vimentin showed a prognostic value for patients with MBC, respectively (E‐cadherin, AUC = 0.637, Fig. A; vimentin, AUC = 0.642, Fig.…”

Section: Resultssupporting

confidence: 92%

Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer

et al. 2019

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Background The molecular phenotype of circulating tumor cells (CTCs) was associated with clinical outcome of patients with breast cancer. CTCs isolated from patients with metastatic breast cancer (MBC) display a unique microRNA (miRNA) expression profile. The aim of this study was to enhance the prognostic accuracy of the CTC phenotype in patients with MBC, by incorporating miRNA into a combined prediction model. Subjects, Materials, and Methods CTCs were detected by CellSearch and enriched by magnetic cell sorting. miRNA deep sequencing and quantitative polymerase chain reaction were used to screen and verify potentially CTC‐specific miRNA candidates. Patients with MBC were enrolled from two independent cohorts, and overall survival (OS) and chemotherapy response were analyzed. Results We screened and identified that miR‐106b was an upregulated molecule in patients with MBC with CTC ≥5/7.5 mL (n = 16) compared with patients with CTC = 0/7.5 mL (n = 16) and healthy donors (n = 8). The expression of CTC‐specific miR‐106b correlated with vimentin and E‐cadherin in CTC and acted as an independent factor for predicting OS (hazard ratio 2.157, 95% confidence interval [CI] 1.098–4.239, p = .026). Although CTC‐specific miR‐106b, E‐cadherin, and vimentin showed a prognostic potential independently, the prognostic performance for OS based on the combination of three markers was significantly enhanced in Cohort 1 (area under the curve [AUC] 0.752, 95% CI 0.658–0.847, n = 128) and further validated in Cohort 2 (AUC 0.726, 95% CI 0.595–0.856, n = 91). Besides, a combined model incorporating miR‐106b was associated with therapy response. Conclusion The phenotypic assemblies of CTC incorporating miR‐106b show enhanced prognostic accuracy of overall survival in patients with MBC. Implications for Practice In order to enhance the prognostic accuracy of the circulating tumor cell (CTC) phenotype in patients with metastatic breast cancer (MBC), this study screened and identified a CTC‐specific microRNA (miRNA), miR‐106b, as an upregulated molecule based on the comparison of miRNA profile between CTCs, primary tumors, and healthy blood donors. By incorporating miR‐106b into a combined prediction model, the prognostic accuracy of the CTC phenotype for patients with MBC was greatly improved in both the training and validation cohorts. This work provides clinical evidence supporting the prognostic potential of CTC‐specific miRNA for patients with MBC. These results indicate that developing CTC‐specific miRNAs as new biomarkers will help to further optimize personalized therapy.

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Section: Resultssupporting

confidence: 92%

Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer

et al. 2019

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“…Studies have demonstrated the vital functionality of EMT during cancer development as well as in GBC progression, with its deregulation facilitating tumor metastasis [24,25]. E-cadherin and Vimentin are considered as principal biomarkers of EMT; however, E-cadherin is commonly disoriented along the progression of EMT [26]. A former study demonstrated a correlation of loss of E-cadherin expression with promoted invasive capacity and high tumor grade and poor prognosis [27].…”

Section: Discussionmentioning

confidence: 99%

Up-regulated microRNA-33b inhibits epithelial–mesenchymal transition in gallbladder cancer through down-regulating CROCC

Wei

et al. 2020

Bioscience Reports

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Gallbladder cancer (GBC) is a relatively rare but fatal gastrointestinal tumor. The microRNA-33b (miR-33b), a member of miR-33 family, is reported to function as a tumor suppressor in various cancers. Notably, miR-33 was predicted to target CROCC based on microarray-based analysis. Hereby, we aimed to characterize the effect of miR-33b on epithelial–mesenchymal transition (EMT) in GBC and the potential mechanism involved with the regulation of CROCC. In GBC cell lines, miR-33b expressed at low levels, and CROCC expressed at high levels, with enhanced EMT process. To further examine the specific mechanism of miR-33b and CROCC in GBC, the GBC cells were treated with the miR-33b mimic/inhibitor or siRNA-CROCC to assess the expression alteration of EMT-related genes and cell proliferation, migration, and invasion. MiR-33b was verified to target and down-regulate the expression of CROCC. The miR-33b up-regulation or CROCC silencing was observed to increase the level of E-cadherin but decrease the levels of N-cadherin and Vimentin, corresponding to impeded cell proliferation, migration, invasion, EMT, and tumor growth. The findings suggest that miR-33b up-regulation hinders GBC development through down-regulating CROCC, which was achieved by inhibition of EMT. The present study may provide an insight on a novel target for GBC treatment.

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“…Vimentin and E-cadherin were regarded as major proteins related with epithelial-mesenchymal transition and clinical outcome. 24 Western blot assay showed that concomitant drugs treatment for MDA-MB-231 cells could significantly downregulate Vimentin expression and up-regulate E-cadherin expression ( Figure 4E and F), which suggested that it is more effective for the treatment of CLBC when using concomitant drugs than single drug.…”

Section: Targeting Pik3cg In Combination With Ptx Significantly Supprmentioning

confidence: 97%

<p>Targeting PIK3CG in Combination with Paclitaxel as a Potential Therapeutic Regimen in Claudin-Low Breast Cancer</p>

Chang¹,

Ling²,

Liu³

et al. 2020

CMAR

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Purpose: Molecular targeting is a powerful approach for aggressive claudin-low breast cancer (CLBC). Overexpression of PI3K catalytic subunit gamma (PIK3CG) in human CLBC is offering a promising opportunity for targeted therapies. We utilized a specific inhibitor of PIK3CG combined with paclitaxel (PTX) to treat CLBC cells in vitro and in vivo. Patients and Methods: The tumor cells growth and apoptosis in vitro were analyzed by CCK8, plate clone formation assay, tumorsphere assay, Hoechst staining and flow cytometry. The invasion and metastasis ability of tumor cells in vitro were investigated by wound healing and transwell experiments. Critical gene expression levels were checked by qRT-PCR and Western blot. Xenograft models with CLBC cell lines in SCID mice were established to investigate the effect of combined drugs in vivo. Results: We identified that PIK3CG was a potential therapeutic target for CLBC patients. Targeting PIK3CG potentiated CLBC cells growth inhibition in 2D and 3D cultures by PTX. Inhibition of PIK3CG activation could enhance CLBC cells apoptosis and migration suppression induced by PTX. Manipulating autophagy was a validated approach for the use of PIK3CG inhibitor. Using CLBC xenograft mice model, we found that CLBC tumors in vivo could be well treated by combined drugs of PIK3CG inhibitor and PTX. Conclusion: We demonstrated that PIK3CG was a potential target for the therapy of CLBC and inhibition of PIK3CG activation could reinforce the therapeutic effect of this aggressive disease by PTX. The combined use of PIK3CG inhibitor and PTX might be a potential regimen for treating this subtype of breast cancer.

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Epithelial Paradox: Clinical Significance of Coexpression of E-cadherin and Vimentin With Regard to Invasion and Metastasis of Breast Cancer

Cited by 70 publications

References 33 publications

Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer

Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer

Up-regulated microRNA-33b inhibits epithelial–mesenchymal transition in gallbladder cancer through down-regulating CROCC

<p>Targeting PIK3CG in Combination with Paclitaxel as a Potential Therapeutic Regimen in Claudin-Low Breast Cancer</p>

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