Table I.

Overview of previous literature investigating the function of MIF and/or CD74 in carcinogenesis, prognosis, proliferation, invasion, angiogenesis and reported responses to targeted therapy.

Cancer type	Carcinogenesisa, refs.	Prognosisb, refs.	Proliferationc, refs.	Invasiond, refs.	Angiogenesise, refs.	Therapyf, refs.
Adenoid cystic carcinoma				4		45
Bladder					50
Breast	12				49
Cervical	13
Colorectal		11	41	11,41	11	56
Gastric	18	33,34	37
Glioma	22		42
Head and neck	24,25,26,15	30,15		30,43,45		43
Liver	21,23	23,29	21,40		53
Lung		28		10	51,52	57
Melanoma	20	31	31		54	56
Multiple myeloma						59
Neuroblastoma				44
Pancreatic	19	32		32
Prostate			14	14		58

^aHigh MIF expression in tumor tissue or high MIF level in serum associated with carcinogenesis.

^bHigh MIF level (tumor or serum) correlated with short patient survival time.

^cFunction of MIF in proliferation, as reported using MIF-silencing strategies (21,31,41), MIF inhibition by antagonist (42,43), MIF or CD74 neutralizing antibodies (14), MIF knock-in (40) and recombinant MIF (40).

^dInvolvement of Ras-related C3 botulinum toxin substrate 1 (10), F-actin (41), N-Myc, Ras, cMet, tropomyosin receptor kinase B (44) and matrix metalloproteinase-9 (46) in MIF-induced invasion.

^eFunction of interleukin-8 (49), vascular endothelial growth factor (50,52), CXC (51), chemokine (C-X-C motif) ligand 8 (52) and hypoxia-induced factor-1α (55) in the MIF-mediated angiogenesis.

^fInhibition of the MIF/CD74 signaling pathway using small molecule inhibitors (43,46,56,57) MIF (58) and CD74 (59) neutralizing antibodies. MIF, migration inhibitory factor; CD, cluster of differentiation.