Control of the Autophagy Maturation Step by the MAPK ERK and p38: Lessons from Environmental Carcinogens

Corcelle, Elisabeth; Djerbi, Nadir; Mari, Mireille; Nebout, Marielle; Fiorini, Céline; Fénichel, Patrick; Hofman, Paul; Poujeol, Philippe; Mograbi, Baharia

doi:10.4161/auto.3424

Cited by 174 publications

(148 citation statements)

References 17 publications

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“…This study showed that resveratrol activated P38 and ERK, but not Akt/mTOR signaling, resulting in the induction of autophagy and the reduction of cell viability. Regarding the function of P38 MAPK in autophagy, abrogation of P38 by chemical inhibitors has been reported to be sufficient to interfere with the normal autophagic maturation step (22,23). Our study showed that P38 was a contributing factor to resveratrol-induced autophagy.…”

Section: Discussionmentioning

confidence: 53%

Resveratrol-induced autophagy in human U373 glioma cells

Yamamoto¹,

Suzuki²,

Himeno³

2010

Oncology Letters

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Abstract. Autophagy is an intracellular protein transport process leading to the degradation of organelles and long-lived proteins in eukaryotes. The down-regulation of autophagy observed in cancer cells has been associated with tumor progression. This study investigated autophagy induced by resveratrol, a natural compound, in human glioma cells. Glioma cells were exposed to resveratrol, and the cell growth and autophagic level were evaluated. Resveratrol inhibited growth and induced cell death in U373 glioma cells. When treated with resveratrol, glioma cells stably expressing GFP fused to LC3, recruited more GFP-LC3-labeled autophagosomes, and the percentage of cells with GFP-LC3-labeled autophagosomes increased. Furthermore, in resveratroltreated glioma cells, pretreatment with P38 or ERK1/2 inhibitors reduced the autophagic level, suggesting that resveratrol-induced autophagy was positively regulated by P38 and the ERK1/2 pathway. The Akt/mTOR pathway was not involved in resveratrol-induced autophagy. Our results suggest that resveratrol has an anticancer effect on glioma cells by inducing autophagy.

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Section: Discussionmentioning

confidence: 53%

Resveratrol-induced autophagy in human U373 glioma cells

Yamamoto¹,

Suzuki²,

Himeno³

2010

Oncology Letters

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“…ERK1/2 is not only transiently activated during starvation-induced autophagy 32 but also involved in the formation and the maturation of autophagosomes. 33 Especially, we propose that ERK1/2 may act as a survival signal in Atg5-deficient cells to overcome environmental stress during cell death triggered by oxidative stress. Thus, Atg-dependent autophagic cell death may be further classified as ERK1/2-dependent and -independent cell death.…”

Section: Discussionmentioning

confidence: 96%

Compensatory activation of ERK1/2 inAtg5-deficient mouse embryo fibroblasts suppresses oxidative stress-induced cell death

Pyo

Nah²,

Kim³

et al. 2008

Autophagy

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“…MAPKs are involved in membrane trafficking, and thus control key steps of phagolysosome biogenesis [44][45][46] and regulate autophagy pathway. 47,48 Some intracellular pathogens hijack MAPK signaling pathways in favor of their survival. For example, intracellular replication of Mycobacterium avium is enhanced by p38 activation, whereas ERK activation has the opposite effect.…”

Section: Discussionmentioning

confidence: 99%

Intracellular colon cancer-associated Escherichia coli promote protumoral activities of human macrophages by inducing sustained COX-2 expression

Raisch

Rolhion

Dubois

et al. 2015

Laboratory Investigation

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Intestinal dysbiosis has been reported in patients with colorectal cancer, and there is a high prevalence of Escherichia coli belonging to B2 phylogroup and producing a genotoxin, termed colibactin. Macrophages are one of the predominant tumor-infiltrating immune cells supporting key processes in tumor progression by producing protumoral factors such as cyclooxygenase-2 (COX-2). Here, we investigated whether B2 E. coli colonizing colon tumors could influence protumoral activities of macrophages. In contrast to commensal or nonpathogenic E. coli strains that were efficiently and rapidly degraded by macrophages at 24 h after infection, colon cancer-associated E. coli were able to resist killing by human THP-1 macrophages, to replicate intracellularly, and to persist inside host cells until at least 72 h after infection. Significant increases in COX-2 expression were observed in macrophages infected with colon cancer E. coli compared with macrophages infected with commensal and nonpathogenic E. coli strains or uninfected cells at 72 h after infection. Induction of COX-2 expression required live bacteria and was not due to colibactin production, as similar COX-2 levels were observed in macrophages infected with the wild-type colon cancer-associated E. coli 11G5 strain or a clbQ mutant unable to produce colibactin. Treatment of macrophages with ofloxacin, an antibiotic with intracellular tropism, efficiently decreased the number of intracellular bacteria and suppressed bacteria-induced COX-2 expression. This study provides new insights into the understanding of how tumor-infiltrating bacteria could influence cancer progression through their interaction with immune cells. Manipulation of microbes associated with tumors could have a deep influence on the secretion of protumoral molecules by infiltrating macrophages. Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies worldwide, making it the fourth most common cause of cancer deaths throughout the world. 1 CRC is a heterogeneous disease, including at least three major forms: hereditary, sporadic, and colitis-associated CRC. A large body of evidence indicates that genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle deeply affect CRC onset. 2,3 In addition to these factors, gut microbiota dysbiosis has been reported in CRC patients. [4][5][6][7][8][9] Recent pyrosequencing analysis of CRC-associated bacterial microbiota has revealed dysbiosis with, in particular, overrepresentation of Fusobacterium and Bacteroides. [10][11][12][13][14] In addition, our group and others have shown that colonic adenomas, carcinomas, and the mucosa of CRC patients are abnormally colonized by Escherichia coli belonging to the B2 phylogroup, with a high prevalence of E. coli producing a genotoxin, termed colibactin, encoded by the pks genomic island. [15][16][17][18][19][20] It has been recently demonstrated that cells that survive infection with colibactin-producing E. coli display hallmarks of cellular senescence accompanied with productio...

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Control of the Autophagy Maturation Step by the MAPK ERK and p38: Lessons from Environmental Carcinogens

Abstract: Previously published online a an Autophagy E-publication: http://www.landesbioscience.com/journals/autophagy/abstract.php?id=3424 KEY WORDSmacroautophagy, autolysosomal maturation, environmental carcinogen, ERK, P38, Sertoli cells ACKNOWLEDGEMENTS

Cited by 174 publications

References 17 publications

Resveratrol-induced autophagy in human U373 glioma cells

Resveratrol-induced autophagy in human U373 glioma cells

Compensatory activation of ERK1/2 inAtg5-deficient mouse embryo fibroblasts suppresses oxidative stress-induced cell death

Intracellular colon cancer-associated Escherichia coli promote protumoral activities of human macrophages by inducing sustained COX-2 expression

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