Table 1.

UPR involvement in cancers.

UPR linked to cancer	Cancer type	Branch of the UPR	References
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]