DEDD Interacts with PI3KC3 to Activate Autophagy and Attenuate Epithelial–Mesenchymal Transition in Human Breast Cancer

Lv, Qi; Wang, Wei; Xue, Jianfei; Hua, Fang; Mu, Rong; Lin, Heng; Yan, Jun; Lv, Xin; Chen, Xiaoguang; Hu, Zhuo Wei

doi:10.1158/0008-5472.can-11-3832

Cited by 151 publications

(125 citation statements)

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“…Several reports demonstrated that autophagy was involved in the EMT progress of some cell lines or tumor tissues, [39][40][41][42] and the embryonic EMT was similar to the transformation of cell phenotype during carcinoma progression. 43 Thus, we did perform the evaluation of E-Cadherin, N-Cadherin and laminin expression following the treatment of RAPA and 3-MA (Figs.…”

Section: Discussionmentioning

confidence: 99%

Autophagy functions on EMT in gastrulation of avian embryo

Wang

et al. 2014

Cell Cycle

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y These authors contributed equally to this work.Keywords: autophagy, Atg7, EMT and chick embryo, gastrulation Abbreviations: 3-MA, 3-Methyladenine; BF, bright-field; DAPI, 49-6-Diamidino-2-phenylindole; EB, embryoid bodies; E-Cad, E-cadherin; EMTs, epithelial-mesenchymal transitions; GFP, green fluorescent protein; HN, Hensen's node; MAPILC3(LC3), microtubule-associated protein 1 light chain 3; mTOR, mammalian target of rapamycin; N-Cad, N-cadherin; NT, neural tube; PBS, phosphate-buffered saline; PCD, Programmed cell death; PD, idiopathic Parkinson's Disease; PI3K, phosphoinositide-3-kinase; PPIA, peptidylprolyl isomerase A; PS, primitive streak; RAPA, Rapamycin; RT-PCR, reverse transcription PCR; shh, sonic hedgehog.Autophagy is important for cell renewing for its contribution to the degradation of bulk cytoplasm, long-lived proteins, and entire organelles and its role in embryonic development is largely unknown. In our study, we investigated the function of autophagy in gastrulation of the chick embryo using both in vivo and in vitro approaches, especially in the EMT process, and we found that autophagy gene Atg7 was expressed on the apical side of the ectoderm and endoderm. Over-expression of Atg7 could enhance the expression of Atg8 and the E-cadherin, the latter of which is a crucial marker of the EMT process. We also found that the disturbance of autophagy could retard the development of chick embryos in HH4 with shorter primitive steak than that in the control group, which is a newly formed structure during EMT process. So we assumed that autophagy could affect EMT process by adhesion molecule expression. Moreover, more molecules, such as slug, chordin, shh et., which were all involved in EMT process, were detected to address the mechanism of this phenomena. We established that the inhibition of autophagy could cause developmental delay by affecting EMT process in gastrulation of chick embryos.

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Section: Discussionmentioning

confidence: 99%

Autophagy functions on EMT in gastrulation of avian embryo

Wang

et al. 2014

Cell Cycle

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“…5,29 Transient transfection was performed using Lipofectamine2000 (Invitrogen, 11668019) according to the manufacturer's instructions. To generate MDA-MB-231 cells stably expressing the pCMV6-AN-MYC and the MYCtagged SLC9A3R1 plasmids were both transfected into MDA-MB-231 cells.…”

Section: Reagentsmentioning

confidence: 99%

“…To generate MDA-MB-231 cells stably expressing the pCMV6-AN-MYC and the MYCtagged SLC9A3R1 plasmids were both transfected into MDA-MB-231 cells. After 24 h of transfection, stable transfectants were selected using neomycin (Invitrogen, 10131035), 5 and a single clone was amplified using a dilution cloning technique. To generate MCF-7 cells stably expressing the controlshRNA and SLC9A3R1-shRNA plasmids were both transfected into MCF-7 cells.…”

Section: Reagentsmentioning

confidence: 99%

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SLC9A3R1 stimulates autophagy via BECN1 stabilization in breast cancer cells

Liu

et al. 2015

Autophagy

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Abbreviations: BCL2, B-cell CLL/lymphoma 2; CHX, cycloheximide; CQ, chloroquine; EGFR, epidermal growth factor receptor; MAP1LC3/LC3, microtubule-associated protein 1 light chain 3; MTOR, mechanistic target of rapamycin (serine/threonine kinase); PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase; PIK3C3, phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4, phosphoinositide-3-kinase regulatory subunit 4; PTEN, phosphatase and tensin homolog; SLC9A3R1, solute carrier family 9, subfamily A (NHE3, cation proton antiporter 3), member 3 regulator 1; UB, ubiquitin.Autophagy, a self-catabolic process, has been found to be involved in abrogating the proliferation and metastasis of breast cancer. SLC9A3R1 (solute carrier family 9, subfamily A [NHE3, cation proton antiporter 3], member 3 regulator 1), a multifunctional scaffold protein, is involved in suppressing breast cancer cells proliferation and the SLC9A3R1-related signaling pathway regulates the activation of autophagy processes. However, the precise regulatory mechanism and signaling pathway of SLC9A3R1 in the regulation of autophagy processes in breast cancer cells remains unknown. Here, we report that the stability of BECN1, the major component of the autophagic core lipid kinase complex, is augmented in SLC9A3R1-overexpressing breast cancer MDA-MB-231 cells, subsequently stimulating autophagy by attenuating the interaction between BECN1 and BCL2. Initially, we found that SLC9A3R1 partially stimulated autophagy through the PTEN-PI3K-AKT1 signaling cascade in MDA-MB-231 cells. SLC9A3R1 then attenuated the interaction between BECN1 and BCL2 to stimulate the autophagic core lipid kinase complex. Further findings revealed that SLC9A3R1 bound to BECN1 and subsequently blocked ubiquitin-dependent BECN1 degradation. And the deletion of the C-terminal domain of SLC9A3R1 resulted in significantly reduced binding to BECN1. Moreover, the lack of C-terminal of SLC9A3R1 neither reduced the ubiquitination of BECN1 nor induced autophagy in breast cancer cells. The decrease in BECN1 degradation induced by SLC9A3R1 resulted in the activity of autophagy stimulation in breast cancer cells. These findings indicate that the SLC9A3R1-BECN1 signaling pathway participates in the activation of autophagy processes in breast cancer cells.

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“…It was recently demonstrated that ectopic expression of the DEDD gene in the MDA-MB-231 metastatic breast cancer cell line led to the degradation of the EMT inducers Snail and Twist through autophagy activation (30). Reversely, knockdown of DEDD in the MCF7 non-metastatic breast cancer cell line led to autophagy reduction and EMT promotion (30).…”

Section: Role Of Autophagy In Cancermentioning

confidence: 99%

Autophagy: A potential target for thyroid cancer therapy (Review)

Lü

et al. 2014

Molecular and Clinical Oncology

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Abstract. The sharply increasing incidence of thyroid cancer has attracted considerable attention over the last few years. The combination of surgery, radioiodine ablation and thyroid-stimulating hormone suppression is usually efficient for the majority of thyroid tumors. However, advanced thyroid cancer that is recurrent, metastatic and 131 I-refractory, or medullary thyroid cancer, pose a therapeutic challenge. Autophagy is a process that metabolizes damaged cytoplasmic organelles and long-lived proteins in order to recycle cellular materials and maintain homeostasis. It has been confirmed that autophagy plays a dual role during cancer development, progression and treatment, mainly depending on the type and stage of the tumor. Autophagy modulation has become a potential therapeutic target for diverse diseases. The mechanism of thyroid tumorigenesis and cancer progression was largely demonstrated to be correlated with the dysregulation of the Ras/Raf/mitogenactivated protein kinase kinase̸extracellular signal-regulated kinase and the phosphoinositide 3-kinase̸Akt̸mammalian target of rapamycin pathways, as well as with abnormal epigenetic modifications. Those mechanisms are associated with autophagy regulation and may be beneficial for the treatment of advanced thyroid cancer. However, the number of available studies on the role of autophagy in thyroid cancer development, progression and treatment outcome, is currently limited. The aim of this review was to elaborate on the relevant knowledge and future prospectives of autophagy in the treatment of thyroid cancer.

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DEDD Interacts with PI3KC3 to Activate Autophagy and Attenuate Epithelial–Mesenchymal Transition in Human Breast Cancer

Cited by 151 publications

References 48 publications

Autophagy functions on EMT in gastrulation of avian embryo

Autophagy functions on EMT in gastrulation of avian embryo

SLC9A3R1 stimulates autophagy via BECN1 stabilization in breast cancer cells

Autophagy: A potential target for thyroid cancer therapy (Review)

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