The role of the unfolded protein response in cancer progression: From oncogenesis to chemoresistance

• Published in: Biology of the cell 2019-01, Vol.111 (1), p.1-17
• Main Authors: Madden, Emma, Logue, Susan E., Healy, Sandra J., Manie, Serge, Samali, Afshin
• Format: Article
• Language: English
• Subjects: Animals; Cancer; Carcinogenesis - metabolism; Cellular Biology; Chemoresistance; Drug Resistance, Neoplasm - physiology; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum Stress - physiology; Humans; Life Sciences; Protein-Serine-Threonine Kinases - metabolism; Unfolded protein response; Unfolded Protein Response - physiology
• ISSN: 0248-4900; 1768-322X
• DOI: 10.1111/boc.201800050

Tumour cells endure both oncogenic and environmental stresses during cancer progression. Transformed cells must meet increased demands for protein and lipid production needed for rapid proliferation and must adapt to exist in an oxygen‐ and nutrient‐deprived environment. To overcome such challenges, cancer cells exploit intrinsic adaptive mechanisms such as the unfolded protein response (UPR). The UPR is a pro‐survival mechanism triggered by accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER), a condition referred to as ER stress. IRE1, PERK and ATF6 are three ER anchored transmembrane receptors. Upon induction of ER stress, they signal in a coordinated fashion to re‐establish ER homoeostasis, thus aiding cell survival. Over the past decade, evidence has emerged supporting a role for the UPR in the establishment and progression of several cancers, including breast cancer, prostate cancer and glioblastoma multiforme. This review discusses our current knowledge of the UPR during oncogenesis, tumour growth, metastasis and chemoresistance. Review: Tumour progression can be broken into distinct stages starting with transformation, leading to unrestricted cell division, angiogenesis, invasion and metastatic spread. Each of these stages present tumour cells with a specific set of challenges, which must be overcome to progress. In this review article we describe the Unfolded Protein Response (UPR) and outline how tumours co‐opt this adaptive cell stress response pathway to ensure their survival and spread.