Induction of fibronectin by HER2 overexpression triggers adhesion and invasion of breast cancer cells

Jeon, Myeongjin; Lee, Jeongmin; Nam, Seok Jin; Shin, Incheol; Lee, J.E.; Kim, Sangmin

doi:10.1016/j.yexcr.2015.02.019

Cited by 38 publications

(36 citation statements)

References 33 publications

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“…FN is an extracellular matrix glycoprotein involved in the adhesion and migration between cells and matrix, and among cells. Studies have shown that a lower FN level can suppress the occurrence of EMT (Jeon et al 2015). In this study, the dynamic changes in FN levels were investigated by ELISA, it was also found that CK or DDP alone or their combination could reduce the level of FN, further indicating that the two drugs can inhibit the EMT process, and the effect of their combination should be stronger than that of either alone of them.…”

Section: Effect Of Ck Combined With Cisplatin On Fn Levels In the Supmentioning

confidence: 61%

Effects of ginsenoside compound K combined with cisplatin on the proliferation, apoptosis and epithelial mesenchymal transition in MCF-7 cells of human breast cancer

Zhang

2015

Pharmaceutical Biology

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Context: Breast cancer seriously harms the health of women and there are currently few therapeutic options for patients with breast cancer. Objective: Effects of ginsenoside compound K (CK) in combination with cisplatin (DDP) on the proliferation, apoptosis, and epithelial mesenchymal transition (EMT) of MCF-7 cells were studied. Materials and methods: MCF-7 cells were divided into CK (50 mmol/L) group, DDP (10 mg/L) group, CK (50 mmol/L) +DDP (10 mg/L) group, and control (CON) group. The cells in the CON group were not treated with any drugs. Proliferation, apoptosis, expression of E-cadherin, N-cadherin, vimentin, protein kinase B (Akt), phosphorylated Akt (p-Akt), and level of fibronectin (FN) in MCF-7 cells were detected by methyl thiazolyl tetrazolium (MTT), flow cytometry, western blotting, and enzyme-linked immuno sorbent assay (ELISA), respectively. Results: The proliferation inhibition rates in CK, DDP, and CK + DDP groups at 48 h were 19.18 ± 2.25, 21.34 ± 2.84, and 43.37 ± 5.62, respectively. The apoptosis rates were 2.85 ± 0.56, 13.37 ± 2.28,

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Section: Effect Of Ck Combined With Cisplatin On Fn Levels In the Supmentioning

confidence: 61%

Effects of ginsenoside compound K combined with cisplatin on the proliferation, apoptosis and epithelial mesenchymal transition in MCF-7 cells of human breast cancer

Zhang

2015

Pharmaceutical Biology

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“…In addition, FN contributes to endocrine resistance through interaction with β1 integrin and then stimulates PI3K/Akt and MAPK/ERK1/2 signaling pathway in ER-α positive breast cancer cells (18). Recently, we also reported that the FN-induced adhesion and invasion characteristics of breast cancer cells are suppressed by an FN inhibitor (RGD tetrapeptide) (5). Here, we explored whether p53 regulates FN expression in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…The complex of integrin and FN can have modulating effects on various signaling pathways including focal adhesion kinase (FAK), signal transducer and activator of transcription-3 (STAT-3), and mitogen-activated protein kinase (MAPK) pathways that promote cell invasion and metastasis in multiple cancer cells (2)(3)(4). The induction of FN by HER2 overexpression triggers cell adhesion and invasion capacities in breast cancer cells (5). In addition, excessive FN expression is linked to poor metastatic-free survival and overall survival in breast cancer patients (6,7).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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Abstract. 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. In addition, overexpression of wild-type p53 markedly decreased the level of FN expression in p53-mutant breast cancer cells. To examine the mechanism underlying the relationship between p53 and FN expression, we treated MCF7 breast cancer cells with the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate). Our results showed that basal FN expression was increased by TPA treatment in a time-dependent manner. In contrast, the level of p53 expression was decreased by TPA treatment. However, the expression of FN and p53 was not altered by TPA in p53-mutant breast cancer cells. Furthermore, the alterations in FN and p53 expression in response to TPA were prevented by a specific MEK inhibitor, UO126. Finally, we demonstrated that TPA triggers degradation of p53 through the proteasomal pathway in MCF7 cells. TPA-induced FN expression was decreased by the proteasome inhibitor MG132. Under the same condition, p53 protein expression, but not mRNA expression, was reversed by MG132. Taken together, our data demonstrate that the level of FN expression is associated with the status and expression of p53 in breast cancer cells. IntroductionFibronectin (FN) is one of the most abundant adhesive glycoproteins of the extracellular matrix and acts as a substrate for cell adhesion during wound healing and metastasis (1). The complex of integrin and FN can have modulating effects on various signaling pathways including focal adhesion kinase (FAK), signal transducer and activator of transcription-3 (STAT-3), and mitogen-activated protein kinase (MAPK) pathways that promote cell invasion and metastasis in multiple cancer cells (2-4). The induction of FN by HER2 overexpression triggers cell adhesion and invasion capacities in breast cancer cells (5). In addition, excessive FN expression is linked to poor metastatic-free survival and overall survival in breast cancer patients (6,7).The tumor suppressor protein p53 is a transcription factor that can trigger cell cycle arrest, replicative senescence, or apoptosis (8). The induction of p53 expression by a wide variety of cellular stresses such as hypoxia, UV, and cytotoxic drugs is involved in accelerated cellular senescence as well as G1/S and G2/M cell cycle checkpoint activation (9-11). The TP53 gene encoding p53 is the most frequently inactivated gene in human malignancy, and somatic missense mutations of p53 are found in ~50% of human cancers (12). Mutations in the TP53 gene result in loss of wild-type p53 tumor suppressor functions (13). Wild-type p53 upregulates p21, the negative regulator of cyclin-dependent kinases (cdks), whereas mutant p53 enhances cdk1 and increases cell proliferation and s...

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“…The Rho/Rock signaling pathway is involved in lysophosphatidic acid-induced breast cancer cell invasion via MMP activation [34], and regulates three-dimensional cell migration by matrix reorganization [30]. Different modes of tumor cell invasion have distinct requirements for Rho/ROCK signaling and extracellular proteolysis has been reported [18]. These studies of evidence reveal the mechanisms of tumor invasion of the surrounding tissue.…”

Section: Discussionmentioning

confidence: 99%

“…The molecular mechanism for expanding growth and invasion in the luminal subtype, which is ER(+), PgR(+), and HER2(−), and the triple negative subtype, which is ER(−), PgR(−), and HER2(−), of IDC might be different from RhoA/Rock signaling. HER2 overexpression may trigger the acceleration of cell invasion and proliferation of tumor cells, not only by fibronectin [18] but also by RhoA/ROCK signaling. The inhibition of Rho or ROCK function was not effective against the movement of cells with an elongated morphology; this may promote selection for cells that use this mode of mobility [32].…”

Section: Discussionmentioning

confidence: 99%

Roles of Ras Homolog A in Invasive Ductal Breast Carcinoma

Murakami

Nakanishi

Hirotani

et al. 2016

Acta Histochem. Cytochem

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Breast cancer has a poor prognosis owing to tumor cell invasion and metastasis. Although Ras homolog (Rho) A is involved in tumor cell invasion, its role in breast carcinoma is unclear. Here, RhoA expression was examined in invasive ductal carcinoma (IDC), with a focus on its relationships with epidermal-mesenchymal transition (EMT) and collective cell invasion. Forty-four surgical IDC tissue samples and two normal breast tissue samples were obtained. RhoA, E-cadherin, vimentin, and F-actin protein expression were analyzed by immunohistochemistry. RhoA, ROCK, mTOR, AKT1, and PIK3CA mRNA expression were conducted using laser microdissection and semi-nested quantitative reverse transcription-polymerase chain reaction. RhoA expression was stronger on the tumor interface of IDCs than the tumor center (P<0.001). RhoA expression was correlated with ROCK expression only in HER2-subtype IDC (P<0.05). In IDCs co-expressing RhoA and ROCK, F-actin expression was stronger on the tumor interface, particularly at the edges of tumor cells, than it was in ROCK-negative IDCs (P<0.0001). In conclusion, RhoA expression was not correlated with EMT in IDC, but enhanced F-actin expression was localized on the edge of tumor cells that co-expressed ROCK. RhoA/ROCK signaling may be associated with collective cell invasion, particularly in HER2-subtype IDC.

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Induction of fibronectin by HER2 overexpression triggers adhesion and invasion of breast cancer cells

Cited by 38 publications

References 33 publications

Effects of ginsenoside compound K combined with cisplatin on the proliferation, apoptosis and epithelial mesenchymal transition in MCF-7 cells of human breast cancer

Effects of ginsenoside compound K combined with cisplatin on the proliferation, apoptosis and epithelial mesenchymal transition in MCF-7 cells of human breast cancer

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

Roles of Ras Homolog A in Invasive Ductal Breast Carcinoma

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