Abstract
Head and neck squamous cell carcinomas (HNSCC) encompass a heterogeneous group of solid tumors that arise from the upper aerodigestive tract. The tumor cells face multiple challenges including an acute demand of protein synthesis often driven by oncogene activation, limited nutrient and oxygen supply and exposure to chemo/radiotherapy, which forces them to develop adaptive mechanisms such as the Unfolded Protein Response (UPR). It is now well documented that the UPR, a homeostatic mechanism, is induced at different stages of cancer progression in response to intrinsic (oncogenic activation) or extrinsic (microenvironment) perturbations. This review will discuss the role of the UPR in HNSCC as well as in the key processes that characterize the physiology of HNSCC. The role of the UPR in the clinical context of HNSCC will also be addressed.
Highlights
Head and Neck Squamous Cell Carcinomas (HNSCCs) are a group of tumors that arise from the mucosal epithelia of the head and neck
The data presented above indicate that endoplasmic reticulum (ER) stress and Unfolded Protein Response (UPR) signaling play a functional role in HNSCC by regulating key tumor biology processes including progression of the disease and therapy resistance
It has been well established that the UPR can exert positive selection on cancer cells in solid tumors [60,61,121,122,123]
Summary
Head and Neck Squamous Cell Carcinomas (HNSCCs) are a group of tumors that arise from the mucosal epithelia of the head and neck They are often associated with alcohol and tobacco use [1,2] and more recently, for some primary locations, viral etiology (Human Papillomavirus, HPV in oropharynx) [1,2]. Cancer cells experience reduced oxygen and energy supply, oxidative stress, acidosis, which compromise protein folding in the endoplasmic reticulum (ER) and lead to the activation of the UPR [7,8] This activation has been implicated in various processes of tumor cell biology including angiogenesis, treatment resistance, invasion, aggressiveness and inflammation [9]. In the context of HNSCC, chronic UPR activation may represent an interesting aspect for the development of novel therapies
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