Inflammatory signaling cascades and autophagy in cancer

Monkkonen, Teresa; Debnath, Jayanta

doi:10.1080/15548627.2017.1345412

Cited by 159 publications

(128 citation statements)

References 53 publications

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“…Intracellular oxidative stress enhances ROS production significantly and excessive ROS stimulates autophagy . It is apparent that both the initiation and execution of autophagy pathways are associated with the consequences of ROS exposure .…”

Section: Molecular Regulation Of Autophagy Machinerymentioning

confidence: 99%

Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways

Al‐Bari

2020

Annals of the New York Academy of Sciences

207

109

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Macroautophagy is a lysosomal degradative pathway or recycling process that maintains cellular homeostasis. This autophagy involves a series of sequential processing events, such as initiation; elongation and nucleation of the isolation membrane; cargo recruitment and maturation of the autophagosome (AP); transport of the AP; docking and fusion of the AP with a late endosome or lysosome; and regeneration of the lysosome by the autophagic lysosomal reformation cycle. These events are critically coordinated by the action of a set of several key components, including autophagy‐related proteins (Atg), and regulated by intricate networks, such as mechanistic target of rapamycin (mTOR), a master regulator of autophagy, as well as mTOR‐independent signaling pathways. Among mTOR‐independent pathways, the transient receptor potential (TRP) calcium ion channel TRPML (mucolipin) subfamily is emerging as an important signaling channel to modulate lysosomal biogenesis and autophagy. This review discusses the recent advances in elucidating the molecular mechanisms and regulation of the autophagy process. Understanding these mechanisms may ultimately allow scientists and clinicians to control this process in order to improve human health.

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Section: Molecular Regulation Of Autophagy Machinerymentioning

confidence: 99%

Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways

Al‐Bari

2020

Annals of the New York Academy of Sciences

207

109

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“…This correlation between IL-6-mediated carcinogenesis and autophagy may represent an interesting and promising approach to treat iCCA with an inflammatory component. Additionally, there are a large number of studies that relate different pro-inflammatory pathways with ER stress and autophagy [79,81,82].…”

Section: Cholangiocarcinoma Genetic and Epigenetic Alterations And Aumentioning

confidence: 99%

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

Pérez‐Montoyo

2020

Cells

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Autophagy is a multistep catabolic process through which misfolded, aggregated or mutated proteins and damaged organelles are internalized in membrane vesicles called autophagosomes and ultimately fused to lysosomes for degradation of sequestered components. The multistep nature of the process offers multiple regulation points prone to be deregulated and cause different human diseases but also offers multiple targetable points for designing therapeutic strategies. Cancer cells have evolved to use autophagy as an adaptive mechanism to survive under extremely stressful conditions within the tumor microenvironment, but also to increase invasiveness and resistance to anticancer drugs such as chemotherapy. This review collects clinical evidence of autophagy deregulation during cholangiocarcinogenesis together with preclinical reports evaluating compounds that modulate autophagy to induce cholangiocarcinoma (CCA) cell death. Altogether, experimental data suggest an impairment of autophagy during initial steps of CCA development and increased expression of autophagy markers on established tumors and in invasive phenotypes. Preclinical efficacy of autophagy modulators promoting CCA cell death, reducing invasiveness capacity and resensitizing CCA cells to chemotherapy open novel therapeutic avenues to design more specific and efficient strategies to treat this aggressive cancer.

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“…Several studies reported that autophagy could play a role in tumor progression or tumor suppression in different stages of cancers [3,4]. However, the role of autophagy in tumorigenesis is still rudimentary.…”

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confidence: 99%

Development of an autophagy-related gene expression signature for prognosis prediction in prostate cancer patients

Jiang

Luo

et al. 2020

J Transl Med

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Background: Prostate cancer (PCa) is one of the most prevalent cancers that occur in men worldwide. Autophagyrelated genes (ARGs) may play an essential role in multiple biological processes of prostate cancer. However, ARGs expression signature has rarely been used to investigate the association between autophagy and prognosis in PCa. This study aimed to identify and assess prognostic ARGs signature to predict overall survival (OS) and disease-free survival (DFS) in PCa patients. Methods: First, a total of 234 autophagy-related genes were obtained from The Human Autophagy Database. Then, differentially expressed ARGs were identified in prostate cancer patients based on The Cancer Genome Atlas (TCGA) database. The univariate and multivariate Cox regression analysis was performed to screen hub prognostic ARGs for overall survival and disease-free survival, and the prognostic model was constructed. Finally, the correlation between the prognostic model and clinicopathological parameters was further analyzed, including age, T status, N status, and Gleason score. Results: The OS-related prognostic model was constructed based on the five ARGs (FAM215A, FDD, MYC, RHEB, and ATG16L1) and significantly stratified prostate cancer patients into high-and low-risk groups in terms of OS (HR = 6.391, 95% CI = 1.581-25.840, P < 0.001). The area under the receiver operating characteristic curve (AUC) of the prediction model was 0.84. The OS-related prediction model values were higher in T3-4 than in T1-2 (P = 0.008), and higher in Gleason score > 7 than ≤ 7 (P = 0.015). In addition, the DFS-related prognostic model was constructed based on the 22 ARGs (ULK2,

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Inflammatory signaling cascades and autophagy in cancer

Cited by 159 publications

References 53 publications

Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways

Molecular regulation of autophagy machinery by mTOR‐dependent and ‐independent pathways

Therapeutic Potential of Autophagy Modulation in Cholangiocarcinoma

Development of an autophagy-related gene expression signature for prognosis prediction in prostate cancer patients

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