Paclitaxel induces lymphatic endothelial cells autophagy to promote metastasis

Zamora, Audrey; Alvès, Mélinda; Chollet, C.; Therville, Nicole; Fougeray, Tiffany; Tatin, Florence; Franchet, Camille; Gomez‐Brouchet, Anne; Vaysse, Charlotte; Martinez, Laurent O.; Najib, Souad; Guillermet-Guibert, Julie; Lacazette, Éric; Prats, Anne-Catherine; Garmy‐Susini, Barbara

doi:10.1038/s41419-019-2181-1

Cited by 40 publications

(40 citation statements)

References 30 publications

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“…It is possible that oxLDL stimulates autophagy in LEC, which leads to decreased AKT expression. In addition, Zamora et al suggested a negative association between lymphangiogenesis and autophagy [ 61 ]. Future studies are required to investigate the effects of oxLDL treatment on autophagy in LEC.…”

Section: Discussionmentioning

confidence: 99%

Oxidatively Modified LDL Suppresses Lymphangiogenesis via CD36 Signaling

et al. 2021

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Arterial accumulation of plasma-derived LDL and its subsequent oxidation contributes to atherosclerosis. Lymphatic vessel (LV)-mediated removal of arterial cholesterol has been shown to reduce atherosclerotic lesion formation. However, the precise mechanisms that regulate LV density and function in atherosclerotic vessels remain to be identified. The aim of this study was to investigate the role of native LDL (nLDL) and oxidized LDL (oxLDL) in modulating lymphangiogenesis and underlying molecular mechanisms. Western blotting and immunostaining experiments demonstrated increased oxLDL expression in human atherosclerotic arteries. Furthermore, elevated oxLDL levels were detected in the adventitial layer, where LV are primarily present. Treatment of human lymphatic endothelial cells (LEC) with oxLDL inhibited in vitro tube formation, while nLDL stimulated it. Similar results were observed with Matrigel plug assay in vivo. CD36 deletion in mice and its siRNA-mediated knockdown in LEC prevented oxLDL-induced inhibition of lymphangiogenesis. In addition, oxLDL via CD36 receptor suppressed cell cycle, downregulated AKT and eNOS expression, and increased levels of p27 in LEC. Collectively, these results indicate that oxLDL inhibits lymphangiogenesis via CD36-mediated regulation of AKT/eNOS pathway and cell cycle. These findings suggest that therapeutic blockade of LEC CD36 may promote arterial lymphangiogenesis, leading to increased cholesterol removal from the arterial wall and reduced atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Oxidatively Modified LDL Suppresses Lymphangiogenesis via CD36 Signaling

et al. 2021

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“…Various modes of action have been proposed to explain the therapeutic and/or adverse effects of CQ and HCQ in COVID-19 patients, although most of the evidence is based on in vitro studies. CQ is a potent inhibitor of autophagy [20][21][22][23] and cell death 24,25 , affecting distinct cell function 26,27 and survival 28,29 , and its derivative HCQ 30 has similar properties inhibiting autophagy. In vitro experiments in tissue culture have shown that CQ and HCQ can increase endosomal pH, prevent virus-cell fusion, and interfere with glycosylation of the ACE2 receptor and thus the binding of the SARS-CoV-2 S protein to ACE2 31 (Fig.…”

Section: Hcq Exerts Strong Immunomodulatory Effectsmentioning

confidence: 99%

Is hydroxychloroquine beneficial for COVID-19 patients?

et al. 2020

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The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019. As similar cases rapidly emerged around the world1–3, the World Health Organization (WHO) declared a public health emergency of international concern on January 30, 2020 and pronounced the rapidly spreading coronavirus outbreak as a pandemic on March 11, 20204. The virus has reached almost all countries of the globe. As of June 3, 2020, the accumulated confirmed cases reached 6,479,405 with more than 383,013 deaths worldwide. The urgent and emergency care of COVID-19 patients calls for effective drugs, in addition to the beneficial effects of remdesivir5, to control the disease and halt the pandemic.

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“…The matter of CQ, a powerful regulator of endosomal pH in autophagy [10][11][12][13] and cell death 14,15 , affecting distinct cell function 16,17 and survival 18,19 , and of its derivative hydroxychloroquine (HCQ) 20 , has peculiar aspects: they are widely used in patients affected by the COVID-19 disease and reports from hospitals and doctors who treat patients frequently suggest beneficial effects. However, major medical institutions tend to recommend a cautious use, also pointing at dangerous side effects.…”

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confidence: 99%

BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic?

Sharma

Shi

et al. 2020

Cell Death Dis

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Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2). In the light of its rapid global spreading, on 11 March 2020, the World Health Organization has declared it a pandemic. Interestingly, the global spreading of the disease is not uniform, but has so far left some countries relatively less affected. The reason(s) for this anomalous behavior are not fully understood, but distinct hypotheses have been proposed. Here we discuss the plausibility of two of them: the universal vaccination with Bacillus Calmette-Guerin (BCG) and the widespread use of the antimalarial drug chloroquine (CQ). Both have been amply discussed in the recent literature with positive and negative conclusions: we felt that a comprehensive presentation of the data available on them would be useful. The analysis of data for countries with over 1000 reported COVID-19 cases has shown that the incidence and mortality were higher in countries in which BCG vaccination is either absent or has been discontinued, as compared with the countries with universal vaccination. We have performed a similar analysis of the data available for CQ, a widely used drug in the African continent and in other countries in which malaria is endemic; we discuss it here because CQ has been used as the drug to treat COVID-19 patients. Several African countries no longer recommend it officially for the fight against malaria, due to the development of resistance to Plasmodium, but its use across the continent is still diffuse. Taken together, the data in the literature have led to the suggestion of a possible inverse correlation between BCG immunization and COVID-19 disease incidence and severity. Introduction The coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, in December 2019 1-3. Since then, it has spread to most countries throughout the world, with major outbreaks in the United States,

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Paclitaxel induces lymphatic endothelial cells autophagy to promote metastasis

Cited by 40 publications

References 30 publications

Oxidatively Modified LDL Suppresses Lymphangiogenesis via CD36 Signaling

Oxidatively Modified LDL Suppresses Lymphangiogenesis via CD36 Signaling

Is hydroxychloroquine beneficial for COVID-19 patients?

BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic?

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