Colorectal cancer cells respond differentially to autophagy inhibition in vivo

Lauzier, Annie; Normandeau-Guimond, Josiann; Vaillancourt-Lavigueur, Vanessa; Boivin, Vincent; Charbonneau, Martine; Rivard, Nathalie; Scott, Michelle S.; Dubois, Claire M.; Jean, Steve

doi:10.1038/s41598-019-47659-7

Cited by 59 publications

(53 citation statements)

References 76 publications

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“…Additionally, Ra EA et al indicated that TRIM31 could promote Atg5/Atg7-independent autophagy in intestinal cells [51]. In addition, Lauzier A et al showed that ATG5 overexpression could promote the development of cancer in vitro [52]. In our research, the miR-155-5p mimic significantly decreased the expression of ATG5.…”

Section: Discussionsupporting

confidence: 61%

miR-155-5p increases the sensitivity of liver cancer cells to adriamycin by regulating ATG5-mediated autophagy

Qiu

Xia

et al. 2021

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Liver cancer is the sixth most prevalent cancer worldwide and the third leading cause of cancer-related deaths. Adriamycin (ADR) resistance, which often leads to the progression of malignant tumors, is a major treatment obstacle for liver cancer. It has been confirmed that miR-155-5p could reverse drug resistance in human breast cancer. However, the biological function of miR-155-5p in ADR-resistant liver carcinoma (HepG2/ADR) cells remains unclear. miR-155-5p and ATG5 expression was determined by RT-qPCR and western blot. In addition, MTT, flow cytometry, immunofluorescence staining, and western blotting were performed to evaluate the proliferation, apoptosis, and autophagy of liver cancer cells. Finally, the effect of miR-155-5p on the expression of autophagy-related 5 (ATG5) was analyzed by luciferase activity assay, western blot, and RT-qPCR. Our results showed that miR-155-5p was downregulated in HepG2/ADR cells. Increasing the expression of miR-155-5p enhanced the sensitivity of liver carcinoma cells to ADR and promoted apoptosis through inhibition of autophagy in vitro. In addition, the binding site between miR-155-5p and ATG5 was identified, and miR-155-5p could directly regulate ATG5. Finally, ATG5 partially rescued the effect of miR-155-5p on autophagy and the apoptosis of HepG2/ADR cells. In conclusion, our findings showed that miR-155-5p could reverse ADR resistance in liver cancer by targeting ATG5, which may function as a potential target for liver cancer treatment.

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Section: Discussionsupporting

confidence: 61%

miR-155-5p increases the sensitivity of liver cancer cells to adriamycin by regulating ATG5-mediated autophagy

Qiu

Xia

et al. 2021

neo

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“…Is there a therapeutic window during which autophagy inhibition will be most beneficial [392,393]? What are the cellular and cancer contexts in which autophagy inhibition will be therapeutically beneficial [22,394,395,396]? Are there indirect or direct caveats to autophagy inhibition in certain cancer contexts, and how can we minimize them [395,397,398]?…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms Underlying Autophagy-Mediated Treatment Resistance in Cancer

Gorski

2019

Cancers

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Despite advances in diagnostic tools and therapeutic options, treatment resistance remains a challenge for many cancer patients. Recent studies have found evidence that autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation and recycling, contributes to treatment resistance in different cancer types. A role for autophagy in resistance to chemotherapies and targeted therapies has been described based largely on associations with various signaling pathways, including MAPK and PI3K/AKT signaling. However, our current understanding of the molecular mechanisms underlying the role of autophagy in facilitating treatment resistance remains limited. Here we provide a comprehensive summary of the evidence linking autophagy to major signaling pathways in the context of treatment resistance and tumor progression, and then highlight recently emerged molecular mechanisms underlying autophagy and the p62/KEAP1/NRF2 and FOXO3A/PUMA axes in chemoresistance.

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“…ER is shown to increase NAD + levels, stimulate SIRT1, and promote autophagy [176,177]. Therefore, preventing toxic accumulation of protein or organelles and oncogenic signaling through autophagy represents another defensive influence mediated by ER-based strategies against cancer and CRC [178], although different sensitivities for autophagy inhibition in CRC have been described [179]. Importantly, contradictory implications for autophagy and SIRT1 in carcinogenesis and CRC are also found, with oncogenic or tumor suppressive functions depending on the cancer type and the particular background or tumor microenvironment [174,178,180,181].…”

Section: Fundamental Cellular and Molecular Adaptations Induced By Enmentioning

confidence: 99%

Energy Restriction and Colorectal Cancer: A Call for Additional Research

et al. 2020

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Colorectal cancer has the second highest cancer-related mortality rate, with an estimated 881,000 deaths worldwide in 2018. The urgent need to reduce the incidence and mortality rate requires innovative strategies to improve prevention, early diagnosis, prognostic biomarkers, and treatment effectiveness. Caloric restriction (CR) is known as the most robust nutritional intervention that extends lifespan and delays the progression of age-related diseases, with remarkable results for cancer protection. Other forms of energy restriction, such as periodic fasting, intermittent fasting, or fasting-mimicking diets, with or without reduction of total calorie intake, recapitulate the effects of chronic CR and confer a wide range of beneficial effects towards health and survival, including anti-cancer properties. In this review, the known molecular, cellular, and organismal effects of energy restriction in oncology will be discussed. Energy-restriction-based strategies implemented in colorectal models and clinical trials will be also revised. While energy restriction constitutes a promising intervention for the prevention and treatment of several malignant neoplasms, further investigations are essential to dissect the interplay between fundamental aspects of energy intake, such as feeding patterns, fasting length, or diet composition, with all of them influencing health and disease or cancer effects. Currently, effectiveness, safety, and practicability of different forms of fasting to fight cancer, particularly colorectal cancer, should still be contemplated with caution.

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Colorectal cancer cells respond differentially to autophagy inhibition in vivo

Cited by 59 publications

References 76 publications

miR-155-5p increases the sensitivity of liver cancer cells to adriamycin by regulating ATG5-mediated autophagy

miR-155-5p increases the sensitivity of liver cancer cells to adriamycin by regulating ATG5-mediated autophagy

Molecular Mechanisms Underlying Autophagy-Mediated Treatment Resistance in Cancer

Energy Restriction and Colorectal Cancer: A Call for Additional Research

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