Extracellular vesicle packaged LMP1-activated fibroblasts promote tumor progression via autophagy and stroma-tumor metabolism coupling

Wu, Xia; Zhou, Zhuan; Xu, San; Liao, Chaoliang; Chen, Xi; Li, Bo; Peng, Jinwu; Li, Dan; Yang, Lifang

doi:10.1016/j.canlet.2020.03.004

Cited by 109 publications

(92 citation statements)

References 49 publications

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“…Autophagy is a fundamental cellular pathway to eukaryotes that function to maintain homeostasis, whose imbalance will lead to the abnormal accumulation of organelles and even the occurrence of tumors [ 47 , 48 ]. Healthy cells appear to be protected from malignant transformation by proficient autophagy responses [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Carcinogenesis of HPV18 and MNNG in Het-1A Cells through p62-KEAP1-NRF2 and PI3K/AKT/mTOR Pathway

Zhang

Zhao

et al. 2020

Oxidative Medicine and Cellular Longevity

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N-methyl-N´-nitro-N-nitrosoguanidine is a clear carcinogen, increasing evidence that indicates an etiological role of human papillomavirus in esophageal carcinoma. Studies have reported the synergistic effect on environmental carcinogens and viruses in recent years. On the basis of establishing the malignant transformation model of Het-1A cells induced by synergistic of HPV18 and MNNG, this study was to explore the synergistic carcinogenesis of MNNG and HPV. Our research indicated that HPV&MNNG led to a significant increase in the protein-expression levels of c-Myc, cyclinD1, BCL-2, BAX, E-cadherin, N-cadherin, mTOR, LC3II, and p62, with concomitant decreases in p21 and LC3I. HPV18 and MNNG induced accumulation of p62 and its interaction with KEAP1, which promoted NRF2 nuclear translocation. p62 loss prevents growth and increases autophagy of malignant cells by activating KEAP1/NRF2-dependent antioxidative response. In addition, PI3K and p-AKT were stimulated by HPV&MNNG, and PI3K/AKT/mTOR is positively associated with cell proliferation, migration, invasion, and autophagy during malignant transformation. Taken together, MNNG&HPV regulates autophagy and further accelerates cell appreciation by activating the p62/KEAP1/NRF2 and PI3K/AKT/mTOR pathway. MNNG&HPV may improve Het-1A cell autophagy to contribute to excessive cell proliferation, reduced apoptosis, and protection from oxidative damage, thus accelerating the process of cell malignant transformation and leading to cancerous cells.

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Section: Discussionmentioning

confidence: 99%

Synergistic Carcinogenesis of HPV18 and MNNG in Het-1A Cells through p62-KEAP1-NRF2 and PI3K/AKT/mTOR Pathway

Zhang

Zhao

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…In addition to TGF-β, several other EV proteins have been found to regulate CAF differentiation, including the integrin very late antigen-4 (VLA-4) and the virally-encoded oncoprotein latent membrane protein 1 (LMP1) [127,136]. Specifically, VLA-4 has been reported to be expressed at high levels in EVs obtained from melanoma cells and has been reported to trigger ERK1/2 signaling in recipient cells, which results in up-regulation of CAF markers and inflammatory factors [136].…”

Section: Proteinsmentioning

confidence: 99%

“…Specifically, VLA-4 has been reported to be expressed at high levels in EVs obtained from melanoma cells and has been reported to trigger ERK1/2 signaling in recipient cells, which results in up-regulation of CAF markers and inflammatory factors [136]. Interestingly, oncogenic LMP1, encoded by the Epstein-Barr Virus (EBV), has been found to be incorporated into the EVs of virally-infected cells and transferred to recipient fibroblasts, resulting in induction of a CAF phenotype via activation of NF-κB signaling [127]. Further, LMP1 uptake has been reported to promote aerobic glycolysis in CAFs.…”

Section: Proteinsmentioning

confidence: 99%

The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

Shoucair

Mello

Jabalee

et al. 2020

IJMS

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Extracellular vesicles (EVs) play a key role in the communication between cancer cells and stromal components of the tumor microenvironment (TME). In this context, cancer cell-derived EVs can regulate the activation of a CAF phenotype in TME cells, which can be mediated by several EV cargos (e.g., miRNA, proteins, mRNA and lncRNAs). On the other hand, CAF-derived EVs can mediate several processes during tumorigenesis, including tumor growth, invasion, metastasis, and therapy resistance. This review aimed to discuss the molecular aspects of EV-based cross-talk between CAFs and cancer cells during tumorigenesis, in addition to assessing the roles of EV cargo in therapy resistance and pre-metastatic niche formation.

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“…The deregulation of autophagy is currently considered to be one of the characteristic vital features contributing to cancer development. Autophagy plays a dual role in cancer; it can suppress the cancer process or protect cancer cells [ 178 , 179 , 180 ]. In neoplasms, autophagy can be inhibited as well as induced.…”

Section: Mitochondrial Impairment In Parkinson’s Disease and Cancementioning

confidence: 99%

The Links between Parkinson’s Disease and Cancer

et al. 2020

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Epidemiologic studies indicate a decreased incidence of most cancer types in Parkinson’s disease (PD) patients. However, some neoplasms are associated with a higher risk of occurrence in PD patients. Both pathologies share some common biological pathways. Although the etiologies of PD and cancer are multifactorial, some factors associated with PD, such as α-synuclein aggregation; mutations of PINK1, PARKIN, and DJ-1; mitochondrial dysfunction; and oxidative stress can also be involved in cancer proliferation or cancer suppression. The main protein associated with PD, i.e., α-synuclein, can be involved in some types of neoplastic formations. On the other hand, however, its downregulation has been found in the other cancers. PINK1 can act as oncogenic or a tumor suppressor. PARKIN dysfunction may lead to some cancers’ growth, and its expression may be associated with some tumors’ suppression. DJ-1 mutation is involved in PD pathogenesis, but its increased expression was found in some neoplasms, such as melanoma or breast, lung, colorectal, uterine, hepatocellular, and nasopharyngeal cancers. Both mitochondrial dysfunction and oxidative stress are involved in PD and cancer development. The aim of this review is to summarize the possible associations between PD and carcinogenesis.

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Extracellular vesicle packaged LMP1-activated fibroblasts promote tumor progression via autophagy and stroma-tumor metabolism coupling

Cited by 109 publications

References 49 publications

Synergistic Carcinogenesis of HPV18 and MNNG in Het-1A Cells through p62-KEAP1-NRF2 and PI3K/AKT/mTOR Pathway

Synergistic Carcinogenesis of HPV18 and MNNG in Het-1A Cells through p62-KEAP1-NRF2 and PI3K/AKT/mTOR Pathway

The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis

The Links between Parkinson’s Disease and Cancer

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