Molecular regulation of autophagy in a pro-inflammatory tumour microenvironment: New insight into the role of serum amyloid A |
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| Affiliation: | 1. Department of Physiological Sciences, University of Stellenbosch, Stellenbosch, South Africa;2. African Cancer Institute (ACI), Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa;3. Department of Internal Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg Campus, South Africa;1. DNAGENETIX, Medical Diagnostic Laboratory, Athens, Greece;2. 3rd Department of Pediatrics, University General Hospital « Attikon », University of Athens, Greece;3. 1st Department of Pediatrics, Agia Sofia Hospital, National and Kapodistrian University of Athens, Athens, Greece;4. Pediatric Department, University Hospital of Heraklion, Crete, Greece;5. Pediatric Department, University Hospital of Larissa, University of Thessaly, Larissa, Greece;6. 1st Department of Pediatrics, « Hippokratio » General Hospital, Aristotle University, Thessaloniki, Greece;1. Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, India;2. Department of Gastroenterology & Human Nutrition, AIIMS, New Delhi, India;1. Department of Pharmacology, College of Basic Medical Sciences, Changchun, Jilin, China;2. Department of Cardiac Surgery, First Hospital of Jilin University, Changchun, Jilin, China;3. Cancer and Stem Cell Center, First Hospital of Jilin University, Changchun, Jilin, China;4. Department of Ultrasonic Cardiogram, First Hospital of Jilin University, Changchun, Jilin, China;5. Stanford University Medical School, VA Palo Alto Health Care System, Palo Alto, California, USA;1. The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha, Hunan, China;2. Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan, China;3. Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Changsha, Hunan, China;4. Department of Respiratory Medicine and Neurology, Hunan Rongjun Hospital, Changsha, Hunan, China;5. Department of Pathology, Changsha Central Hospital, Changsha, Hunan, China;6. Department of Nuclear Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China;7. Changsha Kexin Cancer Hospital, Changsha, Hunan, China;8. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Hunan, China;9. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China |
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| Abstract: | Chronic inflammation, systemic or local, plays a vital role in tumour progression and metastasis. Dysregulation of key physiological processes such as autophagy elicit unfavourable immune responses to induce chronic inflammation. Cytokines, growth factors and acute phase proteins present in the tumour microenvironment regulate inflammatory responses and alter crosstalk between various signalling pathways involved in the progression of cancer. Serum amyloid A (SAA) is a key acute phase protein secreted by the liver during the acute phase response (APR) following infection or injury. However, cancer and cancer-associated cells produce SAA, which when present in high levels in the tumour microenvironment contributes to cancer initiation, progression and metastasis. SAA can activate several signalling pathways such as the PI3K and MAPK pathways, which are also known modulators of the intracellular degradation process, autophagy. Autophagy can be regarded as having a double edged sword effect in cancer. Its dysregulation can induce malignant transformation through metabolic stress which manifests as oxidative stress, endoplasmic reticulum (ER) stress and DNA damage. On the other hand, autophagy can promote cancer survival during metabolic stress, hypoxia and senescence. Autophagy has been utilised to promote the efficiency of chemotherapeutic agents and can either be inhibited or induced to improve treatment outcomes. This review aims to address the known mechanisms that regulate autophagy as well as illustrating the role of SAA in modulating these pathways and its clinical implications for cancer therapy. |
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| Keywords: | Serum amyloid A Autophagy Cancer Inflammation Cell signalling Treatment resistance |
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