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NF-ΚB2, RÉGULATEUR DE L'AUTOPHAGIE DANS LE CANCER COLORECTAL : IMPLICATION DANS LA SÉNESCENCE INDUITE PAR RAS ET LA CHIMIOTHÉRAPIE

Abstract : Oncogene-induced senescence (OIS) is a tumor suppressor mechanism leading to cell cycle arrest. In response to oncogene Ras expression, we have observed that NF-κB2 is activated and regulates transcriptionally the autophagy, a degradation pathway responsible for the recycling of damaged organelles and necessary for senescence establishment. Moreover, the regulation of autophagy by NF-κB2 occurs also during sn38-induced senescence, a chemotherapy for colorectal cancer treatment. Interestingly, we have demonstrated that cells that escape from OIS still present an activation of NF-κB2. During the OIS escape, the phosphorylation of NF-κB2 on serine 222 is lost and could be responsible for an autophagy defect allowing a decrease of senescence in favor of proliferation recovery. Colorectal cancer is the third leading cause of cancer death in France. It is important to diagnose cancer at early stages in order to increase the probabilities of recovery. Through a proteomic study, we have identified OLFM4 as new marker of the early stages of colorectal tumor. We have showed that the expression of OLFM4 is correlated with Ras mutation in tumors, and is regulated by the Ras-NF-κB2 pathway. All together, these results suggest a major role of NF-κB2 in colorectal cancer. The activation of NF- κB2 could represent a marker of tumoral aggressiveness through the regulation of the senescence-dependent autophagy phenotype and OLFM4 expression.
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https://theses.hal.science/tel-01080402
Contributor : Anne-Marie Plé Connect in order to contact the contributor
Submitted on : Friday, May 22, 2015 - 12:12:08 PM
Last modification on : Wednesday, November 10, 2021 - 3:32:03 PM
Long-term archiving on: : Tuesday, September 15, 2015 - 6:42:52 AM

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  • HAL Id : tel-01080402, version 2

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Audrey Bélanger. NF-ΚB2, RÉGULATEUR DE L'AUTOPHAGIE DANS LE CANCER COLORECTAL : IMPLICATION DANS LA SÉNESCENCE INDUITE PAR RAS ET LA CHIMIOTHÉRAPIE. Biologie cellulaire. Université d'Angers, 2014. Français. ⟨NNT : ⟩. ⟨tel-01080402v2⟩

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