Molecular regulation of autophagy in a pro-inflammatory tumour microenvironment: New insight into the role of serum amyloid A. (June 2021)

• Record Type: Journal Article
• Authors: du Plessis, M.; Davis, T.; Loos, B.; Pretorius, E.; de Villiers, W.J.S.; Engelbrecht, A.M.
• Is Part Of: Cytokine & growth factor reviews. Volume 59(2021)
• Page Start: 71
• Page End: 83
• Publication Date: 2021-06
• Subjects: 3-MA 3-methyladenine -- AMPK AMP-activated protein kinase -- AP1 activating protein 1 -- APP acute phase protein -- APR acute phase response -- ATF4 activating transcription factor 4 -- ATP adenosine triphosphate -- BH3 Bcl-2 homology domain -- C/EBP CCAAt/enhancer binding protein -- DNA deoxyribonucleic acid -- DRAM DNA-damage regulated autophagy modulator -- ECM extracellular matrix -- EGF epidermal growth factor -- EMT epithelial-mesenchymal transition -- ER endoplasmic reticulum -- FOXO3 forkhead box O3 -- FPRL-1 formyl peptide receptor like 1 -- GAIP Ga-interacting protein -- GSK3B glycogen synthase kinase 3B -- HDL high density lipoprotein -- HMGB1 high motility group box 1 -- HSP27 heat shock protein 27 -- IKBa inhibitory KBa -- IKK IkB kinase -- IL interleukin -- IRS insulin receptor substrate -- JAK Janus kinase -- JNK C-Jun N-terminal kinase -- LAMP2A lysosome associated membrane protein 2A -- LPS lipopolysaccharide -- MAPK mitogen activated protein kinase -- MCP-1 macrophage chemotactic protein 1 -- MKK7 MAP kinase kinase 7 -- MMP matrix metalloproteinase -- mRNA messenger RNA -- mTOR mammalian target of rapamycin -- NF-IL6 nuclear factor for IL6 -- NFKB nuclear factor kappa-light-chain-enhancer of activated B cells -- NRF nuclear factor erythroid 2-related factor 2 -- P38IP p38 interacting protein -- PDK1 3′-phosphoinositide dependent kinase 1 -- PE phosphatidylethanolamine -- PI3K phosphatidylinositol-3 kinase -- PIP2 phosphatidylinositol-4, 5 bisphosphate -- PIP3 phosphatidylinositol-3, 4, 5 triphosphate -- PTEN phosphatase and tensin homolog -- RAGE receptor for advanced glycation end products -- RHEB Ras homolog enriched in brain -- RNA ribonucleic acid -- ROS reactive oxygen species -- SAA serum amyloid A -- SAF SAS activating factor -- SAPK stress-activated protein kinase -- SAS SAA activating sequence -- SP1 specificity protein 1 -- SR-BI scavenger receptor class B type 1 -- STAT signal transducer and activator of transcription -- TAM tumour associated macrophage -- TGF-B transforming growth factor B -- TLR toll like receptor -- TME tumour microenvironment -- TNF-a tumour necrosis factor alpha -- TRAF TNF receptor associated factor -- TSC tumour sclerosis protein -- ULK Unc-51 like autophagy activating kinase -- YY1 Ying Yang-1; Serum amyloid A -- Autophagy -- Cancer -- Inflammation -- Cell signalling -- Treatment resistance; Cytokines -- Periodicals; 571.84
• DOI: 10.1016/j.cytogfr.2021.01.007
• Languages: English
• ISSNs: 1359-6101

Abstract

Highlights: Serum amyloid A (SAA) can modulate autophagy through multiple entry points in cancer cells. SAA can modulate autophagy positively or negatively, depending on cell type and cellular context. SAA receptor-binding can modulate autophagy in cancer by activating the PI3K/Akt/mTOR and the MAPK signaling pathways. SAA can regulate autophagy through its role as a pro-inflammatory cytokine. Regulation of autophagy by SAA can influence treatment outcomes, highlighting SAA as a potenital target for cancer treatment. 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.