Induction of SUSD2 by STAT3 Activation Is Associated with Tumor Recurrence in HER2-Positive Breast Cancer.

Sushi domain-containing protein 2 (SUSD2), a transmembrane protein containing a sushi motif, has been reported to have tumor-promoting functions in various types of cancer, including breast cancer. However, the regulatory mechanism of SUSD2 and its function in HER2-positive (HER2+) breast cancer have not been fully identified as yet. In this study, we explored the potential of targeting SUSD2 to overcome trastuzumab (TRZ) resistance in HER2+ breast cancer.

Suppression of Platelet-Derived Growth Factor Receptor-Alpha Overcomes Resistance to Trastuzumab through STAT3-Dependent IL-6 Reduction in HER2-Positive Breast Cancer Cells.

Platelet-derived growth factor receptor (PDGFR) plays an essential role in the proliferation and invasion of malignant cancer cells. However, the functional role of PDGFR alpha (PDGFRA) in HER2-positive (HER2+) breast cancer has not been fully clarified yet. Thus, the objective of this study was to investigate the clinical significance of PDGFRA and the therapeutic potential of PDGFR inhibitors as part of an effort to overcome trastuzumab (TRZ) resistance.

Chemokine (C-C motif) Ligand 2 Is Regulated Through the EGFR/Src Pathway in HER2-positive Breast Cancer Cells.

Background/aim: Chemokine (C-C motif) ligand 2 (CCL2) influences growth and metastasis and is associated with poor prognosis in various cancers. However, the regulatory mechanism of CCL2 induction by human epidermal growth factor receptor 2 (HER2) is not fully understood in breast cancer. Thus, we investigated how CCL2 expression is regulated in HER2-positive (HER2+) breast cancer.

Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages.

Basal-like breast cancer (BLBC) has a clinically aggressive nature. It is prevalent in young women and is known to often relapse rapidly. To date, the molecular mechanisms regarding the aggressiveness of BLBC have not been fully understood.

Entelon ( Seed Extract) Prevents Cancer Metastasis via the Downregulation of Interleukin-1 Alpha in Triple-Negative Breast Cancer Cells.

Interleukin-1 (IL1) is a proinflammatory cytokine and promotes cancer cell proliferation and invasiveness in a diversity of cancers, such as breast and colon cancer. Here, we focused on the pharmacological effect of Entelon (ETL) on the tumorigenesis of triple-negative breast cancer (TNBC) cells by IL1-alpha (IL1A). IL1A enhanced the cell growth and invasiveness of TNBC cells.

Celastrol attenuates the inflammatory response by inhibiting IL‑1β expression in triple‑negative breast cancer cells.

IL‑1 promotes cancer cell proliferation and invasiveness in various malignancies, such as breast and colorectal cancer. In the present study, the functional roles of IL‑1β (IL1B) and the inhibitory effect of celastrol on IL1B expression were investigated in triple‑negative breast cancer (TNBC) cells. The data revealed that celastrol markedly decreased IL1B expression and suppressed TNBC cell proliferation in a dose‑dependent manner.

Inhibition of platelet-derived growth factor receptor synergistically increases the pharmacological effect of tamoxifen in estrogen receptor α positive breast cancer.

The platelet-derived growth factor (PDGF) family, a complex and imperative group of proangiogenic factors, acts as strong cell growth chemokines and is essential for the progression of malignancy in humans. In the present study, it was observed that aberrant PDGFB expression is associated with survival rates in patients with estrogen receptor-positive (ER) breast cancer unlike other subtypes, including PDGFA, PDGFC and PDGFD. Accordingly, the effect of specific PDGF receptor (PDGFR) inhibitors on ER-α breast cancer cells was investigated.

Inhibition of platelet-derived growth factor C and their receptors additionally increases doxorubicin effects in triple-negative breast cancer cells.

Complex of platelet-derived growth factor (PDGF) isoforms and PDGF receptors have important functions in the regulation of growth and survival of various cell types. Herein, it was found that aberrant PDGFC expression is closely associated with survival rates in triple-negative breast cancer (TNBC) patients. In addition, PDGFC expression was identified to be significantly increased in TNBC cells unlike other subtypes such as PDGFA, PDGFB, and PDGFD.

WNT5A augments cell invasiveness by inducing CXCL8 in HER2-positive breast cancer cells.

WNT5A is abnormally increased in a variety of cancers including breast cancer and has an adverse effect on the prognosis. However, the biological function of WNT5A is not fully known in HER2-positive (HER2+) breast cancer. Using public clinical data, we analyzed disease-free survival (DFS) and distant metastasis-free survival (DMFS).

EGFR is a Therapeutic Target in Hormone Receptor-Positive Breast Cancer.

Background/aims: Despite effective therapeutic strategies for treating hormone receptor-positive (HR+) breast cancer, resistance to endocrine therapy that is either de novo or acquired still occurs. We investigated epidermal growth factor receptor (EGFR) as a therapeutic target for overcoming endocrine resistance in HR+ breast cancer models.

Methods: Using clinical data from 2,166 patients who had HR+ breast tumors and received tamoxifen, we analyzed survival rates.

Chemoresistance in the Human Triple-Negative Breast Cancer Cell Line MDA-MB-231 Induced by Doxorubicin Gradient Is Associated with Epigenetic Alterations in Histone Deacetylase.

Chemoresistance is one of the major causes of therapeutic failure in breast cancer patients. In this study, the mechanism of chemoresistance in human triple-negative breast cancer (TNBC) cells (MDA-MB-231) induced by doxorubicin (DOX) gradient was investigated. These DOX-resistant cells showed higher drug efflux rate, increased anchorage-independent growth when cultured in suspension, and increased tumor-forming ability in nude mice, compared to the wild-type MDA-MB-231 cells.

TP53 upregulates α‑smooth muscle actin expression in tamoxifen‑resistant breast cancer cells.

In a previous study, we reported that α‑smooth muscle actin (α‑SMA), one of the mesenchymal marker proteins, is highly expressed in tamoxifen‑resistant breast cancer (TamR) cells. However, the exact mechanism of α‑SMA expression in TamR cells is not fully understood. Here, we investigated the effect of TP53 on α‑SMA expression in breast cancer cells.

Berberine down-regulates IL-8 expression through inhibition of the EGFR/MEK/ERK pathway in triple-negative breast cancer cells.

Background: Interleukin-8 (IL-8) expression is associated with metastasis in a variety of cancer cells.

Purpose: Here, we investigated the regulatory mechanism of IL-8 expression as well as the pharmacological effect of berberine (BBR) on IL-8 expression in triple-negative breast cancer (TNBC) cells.

Methods: The clinical value of IL-8 was analyzed by from a public database [Kaplan‑Meier plotter database.

Formation of size-controllable tumour spheroids using a microfluidic pillar array (μFPA) device.

Spheroids are recognized for replicating the physiological microenvironment of tumours. However, because of the lack of controllability of the spheroid size, the response to anticancer drugs is variable in conventional spheroid culture methods. In this paper, we describe a method to generate several hundreds of spheroids of various types of cancer cells including patient derived cancer cells (PDCs) using a microfluidic device with pillars (diameter: 40 μm, height: 70 μm, center-to-center distance: 140 μm), called a microfluidic pillar array (μFPA) device.

Berberine Suppresses Fibronectin Expression through Inhibition of c-Jun Phosphorylation in Breast Cancer Cells.

Purpose: The exact mechanism regulating fibronectin (FN) expression in breast cancer cells has not been fully elucidated. In this study, we investigated the pharmacological mechanism of berberine (BBR) with respect to FN expression in triple-negative breast cancer (TNBC) cells.

Methods: The clinical significance of FN mRNA expression was analyzed using the Kaplan-Meier plotter database (http://kmplot.

Berberine Suppresses Cell Motility Through Downregulation of TGF-β1 in Triple Negative Breast Cancer Cells.

Background/aims: Transforming growth factor-beta proteins (TGF-βs) are multifunctional growth factors and powerful modulators of the epithelial-mesenchymal transition (EMT) in a variety of cancer types including breast and lung cancer cells. Here, we demonstrated the inhibitory effect of berberine (BBR) on tumor growth and metastasis of triple negative breast cancer (TNBC) cells via suppression of TGF-β1 expression.

Methods: The levels of mRNA expression were analyzed by real-time PCR.

Fibronectin expression is upregulated by PI-3K/Akt activation in tamoxifen-resistant breast cancer cells.

Fibronectin (FN) plays important roles in the EMT in a variety of cancer cell types. However, the mechanism by which FN expression is regulated in tamoxifen-resistant (TamR) breast cancer cells has not yet been fully elucidated. Aberrant FN expression was associated with poor prognosis in patients with luminal type A breast cancer.

Wild-type p53 controls the level of fibronectin expression in breast cancer cells.

Aberrant fibronectin (FN) expression is associated with poor prognosis, cell adhesion, and cell motility in a variety of cancer cells. In this study, we investigated the relationship between p53 and FN expression in breast cancer cells. Basal FN expression was significantly decreased by treatment with the p53 activator III, RITA, in MCF7 breast cancer cells with wild-type p53.

Dimerization of EGFR and HER2 induces breast cancer cell motility through STAT1-dependent ACTA2 induction.

The dimerization of EGFR and HER2 is associated with poor prognosis such as induction of tumor growth and cell invasion compared to when EGFR remains as a homodimer. However, the mechanism for events after dimerization in breast cancer models is not clear. We found that expressions of alpha-smooth muscle actin (ACTA2) and signal transducer and activator of transcription 1 (STAT1) significantly increased with transient or stable overexpression of HER2 in EGFR-positive breast cancer cells.

Silibinin inhibits triple negative breast cancer cell motility by suppressing TGF-β2 expression.

Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that regulates many biological events including cell motility and angiogenesis. Here, we investigated the role of elevated TGF-β2 level in triple negative breast cancer (TNBC) cells and the inhibitory effect of silibinin on TGF-β2 action in TNBC cells. Breast cancer patients with high TGF-β2 expression have a poor prognosis.