Transcriptional regulation of autophagy‐lysosomal pathway in cancer

Chang, Xinzhong; Dong, Ruihua

doi:10.1111/1759-7714.13287

Cited by 6 publications

(3 citation statements)

References 57 publications

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“…mTOR and IGF-1/insulin signalling, calpain activity, and nutrient levels, along with transcriptional regulators can all influence autophagy, and lysosomal genes and protein expression critical to the function of this system. 43,44 Myostatin is a member of the transforming growth factorβ superfamily and has been shown to be a potent negative regulator of muscle mass. 45,46 Myostatin's negative influence on skeletal muscle mass is suggested to be due to its negative impact on AKT signalling, myoblast differentiation, and down-regulation of genes involved in muscle homeostasis.…”

Section: Catabolismmentioning

confidence: 99%

Muscle wasting in cancer: opportunities and challenges for exercise in clinical cancer trials

Fairman

Lønbro

Cardaci

et al. 2021

JCSM Rapid Communications

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Background Low muscle in cancer is associated with an increase in treatment-related toxicities and is a predictor of cancer-related and all-cause mortality. The mechanisms of cancer-related muscle loss are multifactorial, including anorexia, hypogonadism, anaemia, inflammation, malnutrition, and aberrations in skeletal muscle protein turnover and metabolism. Methods In this narrative review, we summarise relevant literature to (i) review the factors influencing skeletal muscle mass regulation, (ii) provide an overview of how cancer/treatments negatively impact these, (iii) review factors beyond muscle signalling that can impact the ability to participate in and respond to an exercise intervention to counteract muscle loss in cancer, and (iv) provide perspectives on critical areas of future research. Results Despite the well-known benefits of exercise, there remains a paucity of clinical evidence supporting the impact of exercise in cancer-related muscle loss. There are numerous challenges to reversing muscle loss with exercise in clinical cancer settings, ranging from the impact of cancer/treatments on the molecular regulation of muscle mass, to clinical challenges in responsiveness to an exercise intervention. For example, tumour-related/treatmentrelated factors (e.g. nausea, pain, anaemia, and neutropenia), presence of comorbidities (e.g. diabetes, arthritis, and chronic obstructive pulmonary disease), injuries, disease progression and bone metastases, concomitant medications (e.g., metformin), can negatively affect an individual's ability to exercise safely and limit subsequent adaptation. Conclusions This review identifies numerous gaps and oppportunities in the area of low muscle and muscle loss in cancer. Collaborative efforts between preclinical and clinical researchers are imperative to both understanding the mechanisms of atrophy, and develop appropriate therapeutic interventions.

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Section: Catabolismmentioning

confidence: 99%

Muscle wasting in cancer: opportunities and challenges for exercise in clinical cancer trials

Fairman

Lønbro

Cardaci

et al. 2021

JCSM Rapid Communications

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“…According to a recent review, more important than understanding the inducers and inhibitors of autophagy in cancer therapy is the identification of transcriptional regulators of this process, the evaluation of transcription factors as regulators of autophagy in response to oncogenic stress and the therapeutic implications of these data [ 258 ]. Some findings provide a rationale for chemotherapy targeting the PI3K/mTOR signaling pathway, providing a potential therapeutic strategy to enhance the efficacy of a dual PI3K/mTOR inhibitor in combination with an autophagy inhibitor for the treatment of CRC [ 259 ].…”

Section: Autophagy and Igf System: Implications For Therapy In Crcmentioning

confidence: 99%

Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia

Kasprzak

2023

IJMS

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Colorectal cancer (CRC) is one of the most common human malignancies worldwide. Along with apoptosis and inflammation, autophagy is one of three important mechanisms in CRC. The presence of autophagy/mitophagy in most normal mature intestinal epithelial cells has been confirmed, where it has mainly protective functions against reactive oxygen species (ROS)-induced DNA and protein damage. Autophagy regulates cell proliferation, metabolism, differentiation, secretion of mucins and/or anti-microbial peptides. Abnormal autophagy in intestinal epithelial cells leads to dysbiosis, a decline in local immunity and a decrease in cell secretory function. The insulin-like growth factor (IGF) signaling pathway plays an important role in colorectal carcinogenesis. This is evidenced by the biological activities of IGFs (IGF-1 and IGF-2), IGF-1 receptor type 1 (IGF-1R) and IGF-binding proteins (IGF BPs), which have been reported to regulate cell survival, proliferation, differentiation and apoptosis. Defects in autophagy are found in patients with metabolic syndrome (MetS), inflammatory bowel diseases (IBD) and CRC. In neoplastic cells, the IGF system modulates the autophagy process bidirectionally. In the current era of improving CRC therapies, it seems important to investigate the exact mechanisms not only of apoptosis, but also of autophagy in different populations of tumor microenvironment (TME) cells. The role of the IGF system in autophagy in normal as well as transformed colorectal cells still seems poorly understood. Hence, the aim of the review was to summarize the latest knowledge on the role of the IGF system in the molecular mechanisms of autophagy in the normal colon mucosa and in CRC, taking into account the cellular heterogeneity of the colonic and rectal epithelium.

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“…Natural and synthetic compounds that target early or late pathways, proteasomal inhibitors, protein kinase inhibitors and cytotoxic agents exist, are tested, and have been effective in sensitizing cancer cells [ 183 ]. In addition, several clinical trials are being conducted to gauge the in vivo effects of these drugs [ 184 ]. As CSCs are linked to resistance to therapy, recurrence, and aggressive tumor behavior, understanding the mechanisms underlying the maintenance of CSCs is vital for the development of new therapeutic strategies that target specific populations of CSCs.…”

Section: Targeting Autophagy To Improve Current Cutting-edge Theramentioning

confidence: 99%

Role of Hypoxia-Mediated Autophagy in Tumor Cell Death and Survival

Zaarour

Azakir

Hajam

et al. 2021

Cancers

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Programmed cell death or type I apoptosis has been extensively studied and its contribution to the pathogenesis of disease is well established. However, autophagy functions together with apoptosis to determine the overall fate of the cell. The cross talk between this active self-destruction process and apoptosis is quite complex and contradictory as well, but it is unquestionably decisive for cell survival or cell death. Autophagy can promote tumor suppression but also tumor growth by inducing cancer-cell development and proliferation. In this review, we will discuss how autophagy reprograms tumor cells in the context of tumor hypoxic stress. We will illustrate how autophagy acts as both a suppressor and a driver of tumorigenesis through tuning survival in a context dependent manner. We also shed light on the relationship between autophagy and immune response in this complex regulation. A better understanding of the autophagy mechanisms and pathways will undoubtedly ameliorate the design of therapeutics aimed at targeting autophagy for future cancer immunotherapies.

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Transcriptional regulation of autophagy‐lysosomal pathway in cancer

Cited by 6 publications

References 57 publications

Muscle wasting in cancer: opportunities and challenges for exercise in clinical cancer trials

Muscle wasting in cancer: opportunities and challenges for exercise in clinical cancer trials

Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia

Role of Hypoxia-Mediated Autophagy in Tumor Cell Death and Survival

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