Table 1.

Different chronic diseases and signaling pathways with known associations with the TIPE family of proteins.

Disease	Model	Protein Involved	Targets Associated/Outcome	References
Cancers
Bladder cancer	T24 cells	↑TIPE3	↑PI3K-Akt, ↑MEK-ERK	[31]
Breast cancer	Tissue samples	↑TIPE	tumor progression	[8]
	MDA-MB-231 and MCF-7 cells	↑TIPE2	↓β-catenin, ↓cyclin D1, ↓c-Myc	[36]
	MDA-MB-231 cells transfected into the dorsal flank of female BALB/c nude mice (4–5 weeks old); two groups (vector group and TIPE2 group)		↓tumor growth
	MCF-7 cells	↓TIPE	↑p21	[14]
	MDA-MB-231 and LM2-4175 cells	↓TIPE	↑SNX1, ↑NR4A1, ↑AP2A1, ↓IL5 ↓SRC, ↓MAPT, ↓NEK2, ↓TRAF4, ↓PDCL, ↓GTF2F2, ↓GRAP2, ↓ABL1, ↓AKAP2, ↓GAP43, ↓PIK3CA, ↓EGFR,	[9]
	HS578T and MCF-7 cells	TIPE	-	[37]
	MDA-MB-435 cells MDA-MB 435 cells transfected via tail vein into female BALB/c mice (6–8 weeks old); eight animals in vector group and 12 animals in TIPE group	↓TIPE	↓VEGFR-2, ↓MMP-1, ↓MMP-9	[38]
	MCF-7 and MDA-MB-231	TIPE3	↑MMP2, ↑uPA, ↑AKT, ↑NF-κB	[32]
	MDA-MB-231 cells	↑TIPE	-	[39]
Cervical cancer	Tissue samples	↑TIPE	platinum resistance	[40]
Colon cancer	CACO2 and HCT116 cells	↑TIPE	↑cyclin D1, ↑phospho-Rb	[41]
	HT-29 cells	↓TIPE3	↓PI3K-Akt	[31]
	HCT116 cells	↓TIPE	↑p21	[14]
	HCT116 cells	TIPE	-	[42]
Endometrial cancer	Tumor specimens	↑TIPE	↑Ki-67, ↑MMP-9	[43]
ESCC	TE-1, TE-8, and TE-15 cells	↑TIPE	-	[44]
	Eca109 cells	↓TIPE	↑apoptosis	[6]
Gastric cancer	AGS and HGC-27 cells	↑TIPE2	↓Akt, ↓ERK1/2	[45]
	AGS cells xenografted female BALB/c nude mice (4-week-old); Five mice in each group
	AGS, HGC-27, and SGC-7901 cells	↑TIPE2	↓Akt, ↑GSK3β	[46]
	BGC823 cells	↓TIPE	caspase-3, -8, -9	[47]
	BGC823 cells injected athymic nude mice; four groups containing six animals in each group	↓TIPE	↓tumor growth
	Tissue samples	↑TIPE	↑metastasis, ↓prognosis	[48]
	AGS, BGC-823, and SGC-7901 cells	TIPE1	↓Wnt/β-catenin, ↓MMP-2, ↓MMP-9	[49]
	BGC-823 cells injected through tail vein into male nude mice (5–6 weeks old), four groups (including control group)
	MKN-28, SGC-7901, and MGC-803 cells	↑TIPE	-	[50]
	Tissue samples	↑TIPE	-	[51]
	AGS and HGC-27 cells	↑TIPE2	reversal of EMT	[52]
Glioma	U87, U251, and U373 MG cells	↑TIPE2	↓Wnt/β-catenin, ↓EMT	[53]
HCC	Bel7402, SK-Hep-1, HepG2,	↑TIPE	↓YAP phosphorylation	[7]
	SMMC7721 and Huh7 cells
	Bel7402, SMMC7721, QSG770, HepG2, and HepG2.2.1 cells	TIPE1	↓Rac1	[16]
	Subcutaneously transplanted H22 cells into male BALB/c mice (6–8 weeks old); two groups (including control group) containing at least five mice in each cohort		↓tumor growth and weight
	HepG2 cells	TIPE2	↓Erk1/2-NF-κB	[27]
Lung cancer	H292 and A549 cells	↑TIPE1	↓cyclin D1, cyclin B1, ↓caspase3,	[15]
			↓caspase 8, ↓MMP-2, ↓MMP-9
	A549 cells engrafted into the flank of female BALB/c nude mice; two groups (control group and TIPE1 group) containing five mice in each group	↑TIPE1	↓tumor growth
	H460 and H1299 cells	↑TIPE	↓phosphorylated LATS1	[54]
	A549 cells	↓TIPE	↑p21	[14]
	H1299 cells	TIPE	-	[42]
	Tissue samples	↑TIPE	-	[55]
	H1975 and A549 cells	↑TIPE2	↓Rac1, ↓VEGF	[56]
	Tissue samples	↑TIPE	-	[57]
	H1975 and A549 cells	↑TIPE3	↑Akt, ↑ERK	[30]
	A549 cells transfected into flanks of male BALB/c nude mice (4–6 weeks old), two groups (mock and C-3 flag TIPE3) containing five mice in each group		↑tumor growth
	NCI-H727 cells	↑TIPE3	-	[31]
	Tissue samples		-
	NCI-H460 and A549 cells A549 cells injected into flanks of female BALB/c nude mice (4–6 weeks old); two groups (Control and TIPE group) containing 10 mice in each group	↓TIPE	↓MDM2, ↓RAD51 ↓tumor volume	[58]
Melanoma	MDA-MB-435 cells	↓TIPE	↑NR4A1, ↑AP2A1, ↓TOP2A, ↓EGFR ↓PDCL, ↓GTF2F2, ↓IL5, ↓GRAP2, ↓AKAP2, ↓GAP43, ↓ABL1	[9]
NHL	Tissue samples	↑TIPE2	↑prognosis	[59]
	514 NHL patients and 557 cancer-free controls	TIPE	TIPE polymorphism rs1045241C > T	[60]
Osteosarcoma	143b, LM7, HOS, SaOS-2,	↑TIPE	Modulation of miR-138	[61]
	U2OS and MG-63 cells
	KHOS, 143b, LM7,	↑TIPE	Modulation of miR-99a	[62]
	U2OS and MG-63 cells
	U2OS cells	↓TIPE	↑p21	[14]
Ovarian cancer	Tissue samples	↑TIPE	↓survival	[63]
	OVCAR-3 cells	↓TIPE	G0/G1 cell cycle arrest, ↑beclin 1, ↑LC II	[64]
	Tissue samples	↑TIPE	-	[65]
Pancreatic cancer	Tissue samples	↑TIPE	↑EGFR	[66]
Prostate cancer	PC-3 cells	↓TIPE	↑IGFBP3, ↑NR4A1, ↑AP2A1, ↓IL5,	[9]
			↓MAPT, ↓TOP2A, ↓TRAF4, ↓EGFR,
			↓PDCL, ↓GTF2F2, ↓GRAP2, ↓ABL1,
			↓GAP43, ↓AKAP2, ↓GRIP1
	PC-3 cells	↑TIPE2	↓PI3K/Akt signaling	[67]
	PC-3 cells	↑TIPE	↑MMPs, ↑VEGFR-2	[68]
	PC-3 cells	TIPE	↑autophagy	[69]
Renal cancer	RCC-RS cells	↑TIPE	-	[39]
Thyroid cancer	Tissue samples	↑TIPE	-	[70]
Inflammatory diseases
Atherosclerosis	Ldlr−/− female mice; two groups (wild type and TIPE2−/−) containing eight mice in each group	↓TIPE2	↑JNK, ↑NF-κB, ↑p38	[71]
	VSMCs	↓TIPE2	↓contractile proteins, ↑synthetic capacity for growth factors and cytokines	[72]
Colitis	DSS induced male C57BL/6 mice (8-12 weeks old); two groups (wild type and TIPE2−/−)	↓TIPE2	↓TNF-α, ↓IL-6, ↓IL-12	[73]
	Colonic epithelial cells	↓TIPE	↑cell death	[74]
	DSS-induced mice (8–10 weeks old); two groups (wild type and TIPE2−/−)	↓TIPE	↓survival rate, ↑body weight loss, ↑leukocyte infiltration, ↑bacterial invasion, ↑inflammatory cytokine production in the colon
Rheumatoid arthritis	AA-FLSs	↑TIPE2	↑DR5, ↑caspase, ↓NF-κB	[75]
	Synovial fibroblasts	↑TIPE2	↓Rac signaling	[76]
Infectious diseases
AIH	PBMCs	↓TIPE2	↑ALT, ↑AST	[77]
Hepatitis B	PBMCs	↓TIPE2	↑perforin, ↑granzyme B, ↑IFN-γ	[78]
	PBMCs	↓TIPE2	↑ALT, ↑AST, ↑total bilirubin	[79]
			↑HBV load
	Male C57BL/6 mice (10–12 weeks old); two groups (wild type and TIPE2−/−)	↓TIPE2	↑hepatic inflammation
Hepatitis B liver failure	PBMCs	↑TIPE2	↓TNF-α, ↓IL-6	[80]
Hepatitis B	PBMCs	↑TIPE2	↓IL-6, ↓TNF-α, ↓IFN-γ	[81]
Hepatitis-C induced hepatic inflammation	PBMCs	↓TIPE2	↑TLR signaling	[82]
Listeria infection	HEPA1-6 cells	↓TIPE	↑apoptosis, deregulated Rac1-GTP	[83]
Liver fibrosis	HSC-T6 cells	↑TIPE2	↓β-Catenin, ↓cmyc, ↓cyclin D1	[84]
Neuromuscular and neurodegenerative diseases
Myasthenia Gravis	PBMCs	↓TIPE2	↑IL-6, ↑IL-17, ↑IL-21	[85]
Parkinson’s disease	Dopaminergic neurons	↑TIPE1	↑autophagy, ↓mTOR phosphorylation	[86]
Other diseases
CNV	RPE cells	↓TIPE2	↑TNF-α, ↑IL-1β, ↑VEGF	[87]
Diabetes Mellitus	PBMCs	↑TIPE2	↓TNF-α, ↓IL-6	[88]
Diabetic nephropathy	Mesangial cells	↑TIPE	modulation of NADPH oxidase-mediated signaling pathway	[89]
	Male Sprague-Dawley diabetic rats	↑TIPE	-
Restenosis	VSMCs	↓TIPE2	↑cyclin D1, ↑cyclin D3	[90]
	Male C57BL/6J mice (8–12 weeks old); two groups (wild type and TIPE2−/−)	↓TIPE2	↑severity of disease