Autophagy attenuates endothelial-to-mesenchymal transition by promoting Snail degradation in human cardiac microvascular endothelial cells

Zhang, Jin; Liu, Yanhua; Li, Bingong; Zheng, Zeqi; Ke, Xuan; Hao, Yanqin; Li, Xuelian; Li, Xingxing; Liu, Fuyou; Zhang, Zhiyong

doi:10.1042/bsr20171049

Cited by 38 publications

(33 citation statements)

References 42 publications

(49 reference statements)

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“…Importantly, SNAI1 is degraded through SQSTM1-dependent autophagy, demonstrating a direct mechanism of autophagy-mediated regulation of EMT [164]. In support of this, autophagy-mediated degradation of SNAI1 reduces hypoxia-induced EMT in human cardiac microvascular endothelial cells (HCMECs) [165]. In contrast, starvationinduced autophagy activates EMT and is required for HepG2 and BEL7402 HCC cell invasion in vitro [166].…”

Section: Autophagy Regulates Emtmentioning

confidence: 84%

Mechanisms and context underlying the role of autophagy in cancer metastasis

et al. 2018

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Macroautophagy/autophagy is a fundamental cellular degradation mechanism that maintains cell homeostasis, regulates cell signaling, and promotes cell survival. Its role in promoting tumor cell survival in stress conditions is well characterized, and makes autophagy an attractive target for cancer therapy. Emerging research indicates that autophagy also influences cancer metastasis, which is the primary cause of cancer-associated mortality. However, data demonstrate that the regulatory role of autophagy in metastasis is multifaceted, and includes both metastasis-suppressing and -promoting functions. The metastasis-suppressing functions of autophagy, in particular, have important implications for autophagy-based treatments, as inhibition of autophagy may increase the risk of metastasis. In this review, we discuss the mechanisms and context underlying the role of autophagy in metastasis, which include autophagy-mediated regulation of focal adhesion dynamics, integrin signaling and trafficking, Rho GTPase-mediated cytoskeleton remodeling, anoikis resistance, extracellular matrix remodeling, epithelial-to-mesenchymal transition signaling, and tumor-stromal cell interactions. Through this, we aim to clarify the context-dependent nature of autophagy-mediated metastasis and provide direction for further research investigating the role of autophagy in cancer metastasis.

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Section: Autophagy Regulates Emtmentioning

confidence: 84%

Mechanisms and context underlying the role of autophagy in cancer metastasis

et al. 2018

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“…Defects in mitophagy, a selective form of autophagy that specifically removes dysfunctional mitochondria from cells has also been implicated in AMD pathogenesis [116]. In cancer studies, the activation of autophagy, mitophagy and impaired mitochondrial functionality have been linked to both EMT [117] and EndMT [118], warranting further research into whether parallels exist for RPE and CECs.…”

Section: Metabolic Dysfunction and Autophagy In Amdmentioning

confidence: 99%

EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration

Shu

Butcher

Saint‐Geniez

2020

IJMS

183

138

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Epithelial–mesenchymal transition (EMT) and endothelial–mesenchymal transition (EndMT) are physiological processes required for normal embryogenesis. However, these processes can be hijacked in pathological conditions to facilitate tissue fibrosis and cancer metastasis. In the eye, EMT and EndMT play key roles in the pathogenesis of subretinal fibrosis, the end-stage of age-related macular degeneration (AMD) that leads to profound and permanent vision loss. Predominant in subretinal fibrotic lesions are matrix-producing mesenchymal cells believed to originate from the retinal pigment epithelium (RPE) and/or choroidal endothelial cells (CECs) through EMT and EndMT, respectively. Recent evidence suggests that EMT of RPE may also be implicated during the early stages of AMD. Transforming growth factor-beta (TGFβ) is a key cytokine orchestrating both EMT and EndMT. Investigations in the molecular mechanisms underpinning EMT and EndMT in AMD have implicated a myriad of contributing factors including signaling pathways, extracellular matrix remodelling, oxidative stress, inflammation, autophagy, metabolism and mitochondrial dysfunction. Questions arise as to differences in the mesenchymal cells derived from these two processes and their distinct mechanistic contributions to the pathogenesis of AMD. Detailed discussion on the AMD microenvironment highlights the synergistic interactions between RPE and CECs that may augment the EMT and EndMT processes in vivo. Understanding the differential regulatory networks of EMT and EndMT and their contributions to both the dry and wet forms of AMD can aid the development of therapeutic strategies targeting both RPE and CECs to potentially reverse the aberrant cellular transdifferentiation processes, regenerate the retina and thus restore vision.

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“…Under hypoxic conditions, the EndMT of human cardiac microvascular ECs promoted tube formation. Autophagy provides protective effects against the EndMT of human cardiac microvascular ECs by degrading Snail under hypoxic conditions 51 . In addition, it has been suggested that hypoxia induces EndMT in human coronary ECs via Hif1a-activated Snail, indicating that endocardium-derived ECs undergo EndMT 23 .…”

Section: Role Of Oxidative Stress and Hypoxia In Endmtmentioning

confidence: 99%

Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage

et al. 2020

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Endothelial-to-mesenchymal transition (EndMT) involves the phenotypic conversion of endothelial-to-mesenchymal cells, and was first discovered in association with embryonic heart development. EndMT can regulate various processes, such as tissue fibrosis and cancer. Recent findings have shown that EndMT is related to resistance to cancer therapy, such as chemotherapy, antiangiogenic therapy, and radiation therapy. Based on the known effects of EndMT on the cardiac toxicity of anticancer therapy and tissue damage of radiation therapy, we propose that EndMT can be targeted as a strategy for overcoming tumor resistance while reducing complications, such as tissue damage. In this review, we discuss EndMT and its roles in damaging cardiac and lung tissues, as well as EndMT-related effects on tumor vasculature and resistance in anticancer therapy. Modulating EndMT in radioresistant tumors and radiationinduced tissue fibrosis can especially increase the efficacy of radiation therapy. In addition, we review the role of hypoxia and reactive oxygen species as the main stimulating factors of tissue damage due to vascular damage and EndMT. We consider drugs that may be clinically useful for regulating EndMT in various diseases. Finally, we argue the importance of EndMT as a therapeutic target in anticancer therapy for reducing tissue damage.

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Autophagy attenuates endothelial-to-mesenchymal transition by promoting Snail degradation in human cardiac microvascular endothelial cells

Cited by 38 publications

References 42 publications

Mechanisms and context underlying the role of autophagy in cancer metastasis

Mechanisms and context underlying the role of autophagy in cancer metastasis

EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration

Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage

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