Unfolded protein response and angiogenesis in malignancies

• Published in: Biochimica et biophysica acta. Reviews on cancer Vol. 1878; no. 2; p. 188839
• Main Authors: Izadpanah, Amin, Willingham, Kurtis, Chandrasekar, Bysani, Alt, Eckhard U., Izadpanah, Reza
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2023
• Subjects: ATF6; Humans; IRE1α; Neoplasms; Neovascularization, Pathologic; PERK; Signal Transduction - genetics; Transcriptional Activation; Tumor microenvironment; Unfolded Protein Response; XBP1; VEGFR2; PDGFRa; VCP; ER+ Breast Cancer; BiP; OXPHOS; HIF-1α; PERK; SERCA2a; FLT-1; Unfolded protein response; EIF2α; NF-κB; S1P; PDI; TIE-2; UPR; mTOR; CHOP; TNBC; CSF-1R; GSK; XBP1; EVs; Tumor microenvironment; PLCg; TCA cycle; EIF2AK3; Akt; ER; TME; VEGFA; ERAD; ERN1; S2P; bZIP; ATF; IRE1α; Kit; COP-II; ATF6; PIGF; XBP1s
• ISSN: 0304-419X; 1879-2561
• DOI: 10.1016/j.bbcan.2022.188839

Cellular stress, arising from accumulation of unfolded proteins, occurs frequently in rapidly proliferating cancer cells. This cellular stress, in turn, activates the unfolded protein response (UPR), an interconnected set of signal transduction pathways that alleviate the proteostatic stress. The UPR is implicated in cancer cell survival and proliferation through upregulation of pro-tumorigenic pathways that ultimately promote malignant metabolism and neoangiogenesis. Here, we reviewed mechanisms of signaling crosstalk between the UPR and angiogenesis pathways, as well as transmissible ER stress and the role in tumor growth and development. To characterize differences in UPR and UPR-mediated angiogenesis in malignancy, we employed a data mining approach using patient tumor data from The Cancer Genome Atlas (TCGA). The analysis of TCGA revealed differences in UPR between malignant samples versus their non-malignant counterparts.