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

You, Daeun; Jung, Seung Pil; Jeong, Yu Jeong; Bae, Soo Youn; Lee, Jeong Eon; Kim, Sang-Min

doi:10.5483/bmbrep.2017.50.12.096

Cited by 20 publications

(19 citation statements)

References 31 publications

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“…Another recent study indicated that the dysregulated of FN1 restricted prostate cancer cell invasion [12]. And the enhanced fibronectin expression in tamoxifen-resistant breast cancer cells had been reported by You et al [13]. However, the biological function of FN1 in RAIresistant PTC has few been reported.…”

Section: Introductionmentioning

confidence: 88%

RETRACTED ARTICLE: Downregulation of NEAT1 reverses the radioactive iodine resistance of papillary thyroid carcinoma cell via miR-101-3p/FN1/PI3K-AKT signaling pathway

et al. 2018

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Considering the resistance of papillary thyroid cancer (PTC) 131 I therapy, this study was designed to find a solution at molecular respect. By probing into lncRNA-NEAT1/miR-101-3p/FN1 axis and PI3K/AKT signaling pathway, this study provided a potential target for PTC therapy. 131 I-resistant cell lines were established by continuous treatment with median-lethal 131 I. Bioinformatic analysis was applied to filtrate possible lncRNA/miRNA/mRNA and related signaling pathway. Luciferase reporter assay was employed in the verification of the targeting relationship between lncRNA and miRNA as well as miRNA and mRNA. MTT assay and flow cytometry assay were performed to observe the impact of NEAT1/miR-101-3p/FN1 on cell viability and apoptosis in radioactivity iodine (RAI)-resistant PTC cell lines, respectively. Western blot and qRT-PCR were conducted to measure the expression of proteins and mRNAs in RAI-resistant PTC tissues and cells. Meanwhile, endogenous PTC mice model were constructed, in order to verify the relation between NEAT1 and RAI-resistance in vivo. NEAT1 was over-expressed in RAI-resistant PTC tissues and cell lines and could resist RAI by accelerating proliferation accompanied by suppressing apoptosis. It indicated that overexpressed NEAT1 restrained the damage of RAI to tumor in both macroscopic and microcosmic. Besides, NEAT1/miR-101-3p exhibited a negative correlation by directly targeting each other. The expression of FN1, an overexpressed downstream protein in RAI-resistance PTC tissues, could be tuned down by miR-101-3p, while the decrease could be restored by NEAT1. In conclusion, both in vitro and in vivo, NEAT1 suppression could inhibit 131 I resistance of PTC by upregulating miR-101-3p/FN1 expression and inactivated PI3K/AKT signaling pathway both in vitro and in vivo.

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Section: Introductionmentioning

confidence: 88%

RETRACTED ARTICLE: Downregulation of NEAT1 reverses the radioactive iodine resistance of papillary thyroid carcinoma cell via miR-101-3p/FN1/PI3K-AKT signaling pathway

et al. 2018

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“…Notably, the knockdown of UCA1 inhibits AKT phosphorylation in breast cancer cells (35). Additionally, activation of the PI3K/AKT signaling pathway has been demonstrated to confer resistance to antiestrogens in tamoxifen-resistant breast cancer cells (36). Therefore, it would be useful to determine whether UCA1 is involved in the PI3K/AKT signaling pathway and if it induces tamoxifen resistance in breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA UCA1 confers tamoxifen resistance in breast cancer endocrinotherapy through regulation of the EZH2/p21 axis and the PI3K/AKT signaling pathway

et al. 2019

Int J Oncol

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Tamoxifen is the gold standard for breast cancer endocrinotherapy. However, drug resistance remains a major limiting factor of tamoxifen treatment. Long non-coding (lnc) RNA serves an important role in drug resistance; however, the molecular mechanisms of tamoxifen resistance in breast cancer endocrinotherapy are largely unclear. lncRNA urothelial cancer associated 1 (lncRNA UCA1, UCA1) has been proven to be dysregulated in human breast cancer and promotes cancer progression. In the present study, it was demonstrated that UCA1 was significantly upregulated in breast cancer tissues compared with healthy tissues. Furthermore, the expression level of UCA1 was significantly greater in tamoxifen-resistant breast cancer cells (LCC2 and LCC9) when compared with those in the tamoxifen-sensitive breast cancer cells (MCF-7 and T47D). UCA1 silencing in LLC2 and LLC9 cells increased tamoxifen drug sensitivity by promoting cell apoptosis and arresting the cell cycle at the G 2 /M phase. Notably, the induced overexpression of UCA1 in MCF-7 and T47D cells decreased the drug sensitivity of tamoxifen. The molecular mechanism involved in UCA1-induced tamoxifen-resistance was also investigated. It was identified that UCA1 was physically associated with the enhancer of zeste homolog 2 (EZH2), which suppressed the expression of p21 through histone methylation (H3K27me3) on the p21 promoter. In addition, it was demonstrated that UCA1 expression was paralleled to the phosphorylation of CAMP responsive element binding protein (CREB) and AKT. When LCC2 cells were treated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway inhibitor LY294002, the phosphorylation levels of CREB and AKT were significantly downregulated. Taken together, it was concluded that UCA1 regulates the EZH2/p21 axis and the PI3K/AKT signaling pathway in breast cancer, and may be a potential therapeutic target for solving tamoxifen resistance.

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“…However, we could not demonstrate a direct correlation between FN and p53 scores in the OCCCa/OHGSeCa category, indicating that a p53-independent pathway must regulate FN expression in the tumors, particularly in OCCCa. In fact, FN expression is upregulated through the PI3K/Akt pathway in tamoxifen-resistant breast cancer cells [51].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of fibronectin following loss of p53 function is a poor prognostic factor in ovarian carcinoma with a unique immunophenotype

Yokoi

Matsumoto

Oguri

et al. 2020

Preprint

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Background We previously demonstrated that ovarian high grade serous carcinomas (OHGSeCa) and ovarian clear cell carcinomas (OCCCa) with an HNF-1β+/p53+/ARID1A+ immunophenotype were associated with the worst unfavorable prognosis. To clarify the molecular mechanisms underlying this finding, we focused on alterations in the p53 signaling pathway in these tumors. Methods Changes in cell phenotype and function following knockdown of wild-type p53 (p53-KD) were assessed using OCCCa cells expressing endogenous HNF-1β and ARID1A. The prognostic significance of molecules that were deregulated following p53-KD was also examined using 129 OCCCa/OHGSeCa cases. Results p53-KD cells had increased expression of Snail, phospho-Akt (pAkt), and pGSK3β, and decreased E-cadherin expression, leading to epithelial-mesenchymal transition (EMT)/cancer stem cell (CSC) features. The cells also exhibited acceleration of cell motility and inhibition of cell proliferation and apoptosis. Next generation sequencing revealed that fibronectin (FN) expression was significantly increased in the p53 KD-cells, in line with our observation that wild-type p53 (but not mutant p53) repressed FN1 promoter activity. In addition, treatment of OCCCa cells with FN significantly increased cell migration capacity and decreased cell proliferation rate, independent of induction of EMT features. In clinical samples, FN/p53 scores were significantly higher in OCCCa/OHGSeCa with the HNF-1β+/p53+/ARID1A+ immunophenotype when compared to others. Moreover, high FN/high p53 expression was associated with the worst overall survival and progression-free survival in OCCCa/OHGSeCa patients. Conclusion These findings suggest that upregulation of FN following loss of p53 function may impact the biological behavior of OCCCa/OHGSeCa, particularly in tumors with an HNF-1β+/p53+/ARID1A+ immunophenotype, through alterations in cell mobility and cell proliferation. The accompanying induction of EMT/CSC properties and inhibition of apoptosis due to p53 abnormalities also contribute to the establishment and maintenance of tumor phenotypic characteristics.

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

Cited by 20 publications

References 31 publications

RETRACTED ARTICLE: Downregulation of NEAT1 reverses the radioactive iodine resistance of papillary thyroid carcinoma cell via miR-101-3p/FN1/PI3K-AKT signaling pathway

RETRACTED ARTICLE: Downregulation of NEAT1 reverses the radioactive iodine resistance of papillary thyroid carcinoma cell via miR-101-3p/FN1/PI3K-AKT signaling pathway

Long non‑coding RNA UCA1 confers tamoxifen resistance in breast cancer endocrinotherapy through regulation of the EZH2/p21 axis and the PI3K/AKT signaling pathway

Upregulation of fibronectin following loss of p53 function is a poor prognostic factor in ovarian carcinoma with a unique immunophenotype

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