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| UPR linked to cancer | Cancer type | Branch of the UPR | References |
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| Cancer initiation | CRC | PERK/eIF2α axis activation is associated with the loss of stemness
IRE1α pathway induces intestinal stem cell expansion | [72, 73] |
| Colitis-associated cancer model | XBP1 loss in epithelial cells results in intestinal stem cell hyperproliferation |
| Tumor quiescence and aggressiveness | Prostate cancer | Change in ATF6α, PERK, and IRE1α expression | [60, 61, 71, 74, 75] |
| B-CLL | BiP/GRP78 overexpression triggers survival signals and prevents apoptosis |
| Triple-negative breast cancers | Constitutively active IRE1α/XBP1s axis confers higher aggressiveness due to XBP1-mediated hypoxia-inducible factor-1α activation |
| Glioblastoma (GBM) | IRE1α endoribonuclease activity regulates the extracellular matrix protein SPARC (secreted protein acidic and rich in cysteine) involved in GBM tumor invasion |
| Tumor epithelial-to-mesenchymal transition | Breast tumors thyroid cell glioblastoma (GBM) | Increased expression of XBP1s in metastatic tumors correlates with the EMT inducer SNAIL (snail-related protein)
LOXL2 (lysyl oxidase-like 2)/GRP78 activates the IRE1-XBP1 signaling induce EMT-linked transcription factors expression: SNAI1 (snail family transcriptional repressor), SNAI2, ZEB2 (zinc-finger E-box-binding homeobox 2), and TCF3 (transcription factor 3)
Serpin B3, a serine/cysteine protease inhibitor overexpression, is associated with chronic UPR induction leading to nuclear factor-κB activation and interleukin-6 production
PERK constitutive activation correlates with the overexpression of the TWIST (twist-related protein) transcription factor | [76–78] |
| Tumor angiogenesis | Human head and neck squamous cell carcinoma | Amino acid deprivation promotes tumor angiogenesis through the GCN2/ATF4 pathway | [32, 63, 65, 79–82] |
| Human head and neck squamous cell carcinoma, breast cancer, and glioma cell lines | Glucose deprivation-induced UPR activation promotes upregulation of proangiogenic mediators (VEGF, FGF2, and IL6) and downregulation of several angiogenic inhibitors (THBS1, CXCL14, and CXCL10) through the PERK/ATF4 |
| Colorectal cancer | Hypoxic stress-induced PERK overexpression stimulates the creation of microvessels |
| Glioblastoma (GBM) | IRE1α signaling induce vascular endothelial growth factor-A (VEGF-A), interleukin-1β, and interleukin-6
IRE1α-mediated mRNA cleavage of the circadian gene PERIOD1,92 an important mediator of regulation of the CXCL3 chemokine supports tumor angiogenesis
PERK-ATF4 branch upregulates VEGF in hypoxia |
| Prostatic and glioma cancer cells | Chaperone ORP150 (oxygen-regulated protein 150) controls tumor angiogenesis by promoting the secretion of VEGF |
| Tumor metabolic processes | Triple-negative breast cancer cells | Hypoxia-inducible factor-1α activation, XBP1 upregulates glucose transporter 1 expression promotes glucose uptake of IRE1α, XBP1s downstream activates enzymes of the hexosamine biosynthetic pathway expression | [83] |
| Tumor autophagy | Triple-negative breast cancer cells | PERK/eIF2α/ATF4 pathway activation protect tumor cells through autophagy induction via LC3B (autophagy protein microtubule-associated protein 1 light chain 3b) and ATG5 (autophagy protein 5)
TNF receptor associated factor 2 (TRAF2)/IRE1α activates c-Jun N-terminal protein kinase induces autophagy | [19, 83] |
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