ATG4A promotes tumor metastasis by inducing the epithelial-mesenchymal transition and stem-like properties in gastric cells

Yang, Shiwei; Ping, Yi‐Fang; Jiang, Yuxing; Luo, Xiao-Jing; Zhang, Xia; Bian, Xiu‐Wu; Yu, Ping

doi:10.18632/oncotarget.9827

Cited by 30 publications

(29 citation statements)

References 52 publications

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“…Several works show that defects in the autophagic machinery restrain dissemination and metastatic spreading of cancer [20][21][22]. In line with these facts, inhibition of autophagy reduces FSTL1 (follistatin like 1)-induced EMT in human bronchial epithelial cells [23], whereas ATG4A overexpression significantly promotes EMT in gastric cancer cells [24]. Conversely, there is evidence indicating that autophagy acts to prevent EMT and that the activation of the autophagic machinery may determine reversion of the EMT phenotype in cancer cells [25][26][27][28][29][30][31][32][33][34].…”

Section: Introductionmentioning

confidence: 76%

Autophagy inhibition specifically promotes epithelial-mesenchymal transition and invasion in RAS-mutated cancer cells

et al. 2019

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Macroautophagy/autophagy inhibition is a novel anticancer therapeutic strategy, especially for tumors driven by mutant RAS. Here, we demonstrate that autophagy inhibition in RAS-mutated cells induces epithelial-mesenchymal transition (EMT), which is associated with enhanced tumor invasion. This is at least partially achieved by triggering the NFKB/NF-κB pathway via SQSTM1/p62. Knockdown of ATG3 or ATG5 increases oncogenic RAS-induced expression of ZEB1 and SNAI2/Snail2, and activates NFKB activity. Depletion of SQSTM1 abolishes the activation of the NFKB pathway induced by autophagy inhibition in RAS-mutated cells. NFKB pathway inhibition by depletion of RELA/p65 blocks this EMT induction. Finally, accumulation of SQSTM1 protein correlates with loss of CDH1/E-cadherin expression in pancreatic adenocarcinoma. Together, we suggest that combining autophagy inhibition with NFKB inhibitors may therefore be necessary to treat RAS-mutated cancer.

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Section: Introductionmentioning

confidence: 76%

Autophagy inhibition specifically promotes epithelial-mesenchymal transition and invasion in RAS-mutated cancer cells

et al. 2019

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“…It was hypothesized that overexpression of the regulator of G-protein signaling pathway 1 (RGS1) might promote the transition of stem cells into CSCs [308]. Besides, CSCs are involved in EMT progression via a vast number of mechanisms, including an overactivation of KRAS, STAT3, Rac1, Wnt, Notch, PTEN, ERK, NF-κB signaling pathways, or hypoxic microenvironment [309][310][311][312][313][314][315][316][317][318]. Recently, researchers have proposed the role of CSC-associated protein, leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2), in gastric cancer and EMT initiation [319].…”

Section: Stem Cellsmentioning

confidence: 99%

Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

Baj

Korona-Głowniak

Forma

et al. 2020

Cells

118

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Helicobacter pylori (H. pylori) is one of the most common human pathogens, affecting half of the world's population. Approximately 20% of the infected patients develop gastric ulcers or neoplastic changes in the gastric stroma. An infection also leads to the progression of epithelial-mesenchymal transition within gastric tissue, increasing the probability of gastric cancer development. This paper aims to review the role of H. pylori and its virulence factors in epithelial-mesenchymal transition associated with malignant transformation within the gastric stroma. The reviewed factors included: CagA (cytotoxin-associated gene A) along with induction of cancer stem-cell properties and interaction with YAP (Yes-associated protein pathway), tumor necrosis factor α-inducing protein, Lpp20 lipoprotein, Afadin protein, penicillin-binding protein 1A, microRNA-29a-3p, programmed cell death protein 4, lysosomal-associated protein transmembrane 4β, cancer-associated fibroblasts, heparin-binding epidermal growth factor (HB-EGF), matrix metalloproteinase-7 (MMP-7), and cancer stem cells (CSCs). The review summarizes the most recent findings, providing insight into potential molecular targets and new treatment strategies for gastric cancer.

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“…Some literatures investigate the relationship between autophagy and EMTs using tumor cell lines in pancreatic cancer, cholangiocarcinoma, hepatocellular carcinoma, gastric cancer, glioblastoma, and so on. Yang et al demonstrated that ATG4A promotes the metastasis of gastric cancer cells by inducing EMT via the Notch signaling pathway which is an autophagy‐independent mechanism. Nevertheless, Catalano et al observed that autophagy modulation triggers a molecular switch from a mesenchymal phenotype to an epithelial‐like one in glioblastoma cellular models .…”

Section: Introductionmentioning

confidence: 99%

Knockdown of Beclin‐1 impairs epithelial‐mesenchymal transition of colon cancer cells

Shen

Yin

Deng

et al. 2018

J of Cellular Biochemistry

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Activation of autophagy significantly affects cancer cell behaviors, such as proliferation, differentiation, and invasiveness. Epithelial-to-mesenchymal transition (EMT) as an initial step of malignant transformation of cancer cells was linked to the activation of autophagy, but the detailed molecular mechanisms are still unknown. The present study investigates the effects of Beclin-1, a key molecule involved in activation of autophagy, on EMT of colon cancer cells. The normal colon epithelia cell line of CCD-18Co and six colon cancer cell lines with different expression levels of Beclin-1 were used in this study. The activation of autophagy and EMT markers of cancer cells were monitored by Western blotting and quantitative real-time PCR assay in the presence or absence of rapamycin (autophagy activator) and 3-MA (autophagy inhibitor). The expression of Beclin-1 in selected cell lines was modulated using small interfering RNA, and consequentially EMT markers, and cancer cell behaviors including migration and invasion, were also explored. Activation or inhibition of autophagy in colon cancer cells had positive or negative impacts on the expression of EMT markers and malignant behaviors such as cell migration and invasion. Knockdown of beclin-1 by siRNA apparently inhibited the activation of autophagy induced by rapamycin, consequentially resulted in suppression of EMT and attenuation of invasiveness of colon cancer cells. The results in this study demonstrated an association between activation of autophagy and EMT in colon cancer cells. The results showed suppression of Beclin-1 expression significantly reduced EMT and invasive behaviors in colon cancer cells.

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ATG4A promotes tumor metastasis by inducing the epithelial-mesenchymal transition and stem-like properties in gastric cells

Cited by 30 publications

References 52 publications

Autophagy inhibition specifically promotes epithelial-mesenchymal transition and invasion in RAS-mutated cancer cells

Autophagy inhibition specifically promotes epithelial-mesenchymal transition and invasion in RAS-mutated cancer cells

Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

Knockdown of Beclin‐1 impairs epithelial‐mesenchymal transition of colon cancer cells

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