DIRAS3 regulates the autophagosome initiation complex in dormant ovarian cancer cells

Lü, Zhen; Baquero, Maria T.; Yang, Hailing; Yang, Mengjiao; Reger, Albert S.; Kim, Choel; Levine, Douglas A.; Clarke, Charlotte H.; Liao, Warren S.L.; Bast, Robert C.

doi:10.4161/auto.28577

Cited by 64 publications

(70 citation statements)

References 53 publications

(78 reference statements)

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“…The differential modulation of autophagy by RV and IL‐6 was paralleled by a concordant modulation of the level of ARH‐I. This protein can displace BCL‐2 in the binding to BECLIN 1, thus favoring its interaction with PI3KC3 and thereafter leading to the initiation of autophagy . It is to be noted that the expression of BECLIN 1 was much lower in highly invasive and metastatic subclones than in the non‐invasive subclones of A2780 and SKOV3 ovarian cancer cells .…”

Section: Discussionmentioning

confidence: 95%

Resveratrol inhibits IL‐6‐induced ovarian cancer cell migration through epigenetic up‐regulation of autophagy

Ferraresi

Phadngam

Morani

et al. 2016

Molecular Carcinogenesis

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Interleukin-6 (IL-6), a pro-inflammatory cytokine released by cancer-associated fibroblasts, has been linked to the invasive and metastatic behavior of ovarian cancer cells. Resveratrol is a naturally occurring polyphenol with the potential to inhibit cancer cell migration. Here we show that Resveratrol and IL-6 affect in an opposite manner the expression of RNA messengers and of microRNAs involved in cell locomotion and extracellular matrix remodeling associated with the invasive properties of ovarian cancer cells. Among the several potential candidates responsible for the anti-invasive effect promoted by Resveratrol, here we focused our attention on ARH-I (DIRAS3), that encodes a Ras homolog GTPase of 26-kDa. This protein is known to inhibit cell motility, and it has been shown to regulate autophagy by interacting with BECLIN 1. IL-6 down-regulated the expression of ARH-I and inhibited the formation of LC3-positive autophagic vacuoles, while promoting cell migration. On opposite, Resveratrol could counteract the IL-6 induction of cell migration in ovarian cancer cells through induction of autophagy in the cells at the migration front, which was paralleled by up-regulation of ARH-I and down-regulation of STAT3 expression. Spautin 1-mediated disruption of BECLIN 1-dependent autophagy abrogated the effects of Resveratrol, while promoting cell migration. The present data indicate that Resveratrol elicits its anti-tumor effect through epigenetic mechanisms and support its inclusion in the chemotherapy regimen for highly aggressive ovarian cancers. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 95%

Resveratrol inhibits IL‐6‐induced ovarian cancer cell migration through epigenetic up‐regulation of autophagy

Ferraresi

Phadngam

Morani

et al. 2016

Molecular Carcinogenesis

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“…Targeting of AKT has recently shown promising clinical activity in combination with carboplatin and paclitaxel in a Phase Ib/II study of platinum-resistant ovarian cancer 61 . Expression of markers of autophagy is increased in dormant, drug-resistant tumour nodules found on the peritoneal surface in recurrent disease compared with primary disease 62 , suggesting that targeting autophagic processes may be important in overcoming dormancy in HGSOC.…”

Section: Understand Determinants Of Drug Responsementioning

confidence: 99%

Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

et al. 2015

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High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This ‘roadmap’ for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015.

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“…The clinical relevance of these observations with cell lines and xenografts is supported by observations with primary and "second look" (Lu et al 2014b ). All patients were in a complete clinical remission at the completion of adjuvant chemotherapy defi ned by normal CA-125 level, normal CT scans of the abdomen and pelvis, and a normal physical exam.…”

Section: Autophagy In Ovarian Cancer Dormancymentioning

confidence: 77%

Tumor Dormancy, Quiescence, and Senescence, Vol. 3

2014

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DIRAS3 regulates the autophagosome initiation complex in dormant ovarian cancer cells

Cited by 64 publications

References 53 publications

Resveratrol inhibits IL‐6‐induced ovarian cancer cell migration through epigenetic up‐regulation of autophagy

Resveratrol inhibits IL‐6‐induced ovarian cancer cell migration through epigenetic up‐regulation of autophagy

Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

Tumor Dormancy, Quiescence, and Senescence, Vol. 3

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