Breast cancer cell motility is promoted by 14-3-3γ

Hiraoka, Emiko; Mimae, Takahiro; Ito, Masaoki; Kadoya, Takayuki; Miyata, Yoshihiro; Ito, Akihiko; Okada, Morihito

doi:10.1007/s12282-019-00957-4

Cited by 17 publications

(12 citation statements)

References 30 publications

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“…By participating in numerous signaling pathways, dysregulation of 14-3-3 proteins is involved in many diseases [7,8]. Expression levels of the majority of 14-3-3 isoforms are elevated in many tumors, such as meningioma [77], astrocytoma [78], glioblastoma [79], lung cancer [80,81], breast cancer [82,83], and hepatocellular carcinoma [84,85]. Because 14-3-3σ is a tumor suppressor, its expression in tumors is negatively regulated [77,86].…”

Section: Structure and Function Of 14-3-3 Proteinsmentioning

confidence: 99%

14-3-3 Proteins are Potential Regulators of Liquid–Liquid Phase Separation

Huang

Zheng

et al. 2022

Cell Biochem Biophys

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The 14-3-3 family proteins are vital scaffold proteins that ubiquitously expressed in various tissues. They interact with numerous protein targets and mediate many cellular signaling pathways. The 14-3-3 binding motifs are often embedded in intrinsically disordered regions which are closely associated with liquid-liquid phase separation (LLPS). In the past ten years, LLPS has been observed for a variety of proteins and biological processes, indicating that LLPS plays a fundamental role in the formation of membraneless organelles and cellular condensates. While extensive investigations have been performed on 14-3-3 proteins, its involvement in LLPS is overlooked. To date, 14-3-3 proteins have not been reported to undergo LLPS alone or regulate LLPS of their binding partners. To reveal the potential involvement of 14-3-3 proteins in LLPS, in this review, we summarized the LLPS propensity of 14-3-3 binding partners and found that about one half of them may undergo LLPS spontaneously. We further analyzed the phase separation behavior of representative 14-3-3 binders and discussed how 14-3-3 proteins may be involved. By modulating the conformation and valence of interactions and recruiting other molecules, we speculate that 14-3-3 proteins can efficiently regulate the functions of their targets in the context of LLPS. Considering the critical roles of 14-3-3 proteins, there is an urgent need for investigating the involvement of 14-3-3 proteins in the phase separation process of their targets and the underling mechanisms.

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Section: Structure and Function Of 14-3-3 Proteinsmentioning

confidence: 99%

14-3-3 Proteins are Potential Regulators of Liquid–Liquid Phase Separation

Huang

Zheng

et al. 2022

Cell Biochem Biophys

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“…More recently, Hiraoka et al have shown that pseudopodial protrusion, which is an associated process with tumor cell migration and invasion, are induced in 14-3-3γ-overexpressing breast cancer cells. 21 In our previous study, we had shown a significant reduction of invasion and migration in 14-3-3γ-suppressing A549 and H358 cells, which is involved with inhibition of matrix metalloproteinase (MMP)-2 and MMP-9, through the regulation of EMT. 12 Over the past several decades, there has been a dramatic increase in the studies showing the association of 14-3-3 protein with EMT-related proteins.…”

Section: Discussionmentioning

confidence: 97%

Overexpression of 14-3-3γ Induces the Migration and Invasion of Human Lung Adenocarcinoma A549 Cells

Raungrut

Champoochana

Thongsuksai

et al. 2021

J Health Sci Med Res

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Objective: 14-3-3 gamma (γ) is known to modulate the development and progression of many cancers. However, the evidence in lung cancer is still unclear. In this study, effects of 14-3-3γ on tumor cell migration and invasion were investigated. Material and Methods: A 14-3-3γ expression vector was made and transfected into A549 cells. In-vitro scratch assay and transwell assay were applied to assess migration and invasion, respectively. Western blotting was used to detect expression of proteins related to epithelial–mesenchymal transition.Results: Closing rate of scratch wounds, both in classical and non-classical scratch assay, was significantly increased in 14-3-3γ-overexpressing cells in comparison to the controls. Similarly, by transwell assay, a significant increase in the invasion and migration was shown in the 14-3-3γ-overexpressing cells in comparison to the null vector cells, by approximately 79.2% (p-value=0.002) and 131.2% (p-value<0.001), respectively. In addition, increased 14-3-3γ expression resulted in a significant increase of β-catenin and Snail but not for E-cadherin and vimentin. Conclusion: The study demonstrates the role of 14-3-3γ protein on lung cancer progression via migration and invasion processes, possibly providing a new targeted therapy for non-small cell lung cancer.

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“…Jie Mei et al suggested that YWHAZ promotes the migration of breast cancer cells by adjusting the DAAM1 / RhoA Signaling pathway [29]. Emiko Hiraoka et al demonstrated that YWHAG (also known as 14-3-3γ) promotes the migration activity of BRCA cells [30]. Tumor susceptibility gene BRCA1 is involved in transcriptional regulation, and its over-expression can increase the risk of BRCA [31].…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel gene signature with DDR and EMT difunctionalities for predicting prognosis, immune activity, and drug response in breast cancer

Zhang

et al. 2022

Preprint

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Breast cancer (BRCA) is one of the leading causes of female death worldwide. There are substantial evidences that DNA damage repair (DDR) and epithelial-mesenchymal transition (EMT) are critically related to cancer’s progression and treatment. Nevertheless, it has not been illuminated whether genes with the two functions play a more crucial role in the prognosis, immune and therapy response of BRCA patients. In this study, We identified the prognostic-related genes with both DDR and EMT functions and explored the immune infiltration and chemosensitivity between the different risk groups. The transcriptome expression data and clinical information of BRCA patients were extracted from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The univariate Cox regression analysis was used to screen the prognosis-related DEDGs. The least absolute shrinkage and selection operator (LASSO) Cox regression was performed to construct a prognosis model. Additionally, the multivariate COX regression was conducted to construct a prognostic nomogram. ESTIMATE algorithm, ssGSEA, and the IC50 of chemotherapeutic drugs were used to assess immune activity and responsiveness to chemotherapy. And the prognostic model of six DEDGs were validated in two independent GEO cohorts. The study found that the high-risk group’s patients had significantly lower survival rates than the low-risk group. The immune infiltration levels were lower in the high-risk group. Moreover, patients in the high-risk group were more insensitive to chemotherapeutic agents. This study provides a theoretical framework for BRCA’s treatment and contributing into individualized therapy strategies in BRCA.

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Breast cancer cell motility is promoted by 14-3-3γ

Cited by 17 publications

References 30 publications

14-3-3 Proteins are Potential Regulators of Liquid–Liquid Phase Separation

14-3-3 Proteins are Potential Regulators of Liquid–Liquid Phase Separation

Overexpression of 14-3-3γ Induces the Migration and Invasion of Human Lung Adenocarcinoma A549 Cells

Identification of a novel gene signature with DDR and EMT difunctionalities for predicting prognosis, immune activity, and drug response in breast cancer

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