EGFR-mediated autophagy in tumourigenesis and therapeutic resistance. (28th January 2020)

• Record Type: Journal Article
• Authors: Wu, Min; Zhang, Pinghu
• Is Part Of: Cancer letters. Volume 469(2020)
• Page Start: 207
• Page End: 216
• Publication Date: 2020-01-28
• Subjects: EGFR -- Autophagy regulation -- Tumour suppressor -- Tumour protector -- Chemoresistance -- Therapeutic targets; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2019.10.030
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that links extracellular signals to the control of cell survival, growth, proliferation and differentiation. Due to its frequent overexpression and hyperactivation, EGFR has been a therapeutic target for human malignancies. Unfortunately, the specialized inhibitors of EGFR or EGFR-mediated pathways have not yet achieved the desired clinical effects. Therefore, it is necessary to elucidate the EGFR-mediated molecular basis of tumourigenesis, development and therapeutic resistance and to identify potential therapeutic targets. Interestingly, emerging research has indicated that autophagy is closely related to tumourigenesis, tumour progression and chemoresistance. Both autophagy upregulation and downregulation have been observed in cancers, suggesting its dual oncogenic and tumour suppressor properties during malignant transformation. Importantly, EGFR has been demonstrated to be a critical determinant of whether autophagy has a cytoprotective or cytotoxic effect. Therefore, here, we mainly focus on the function of EGFR in autophagy, especially the potential mechanism. The EGFR-mediated pathways or proteins involved in autophagy regulation include (1) the EGFR-mTOR pathway; (2) the EGFR-RAS pathway; (3) EGFR-Beclin1; (4) the EGFR-STAT3 pathway and (5) EGFR-LAPTM4B (oncoprotein lysosomal-associated transmembrane protein 4B). In addition, we also describe the role of EGFR-mediated autophagy in chemoresistance and tumour therapy. We attempt to summarized the mechanism by which EGFR-mediated signalling pathways participate in regulating autophagy and to investigate how to use the existing knowledge to identify potential cancer therapeutic targets. Highlights: EGFR or EGFR mutation-mediated autophagy plays a critical role in tumorigenesis, tumor progress and therapy resistance. The role of EGFR-mediated autophagy in tumorigenesis and therapy resistance is highly cell-dependent. Regulating EGFR-mediated autophagy might be a new strategy for the treatment of EGFR deregulated tumors.