Table 1. List of PIN1 actions on cellular substrates identified in breast cancer.

Protein	PIN1-binding motifs	Kinase	PIN1 function	Cellular effect/phenotype in BC cells	Synergy between PIN1 inhibition and known drugs	Refs.
AKT/PKB	Thr92, Thr450	ND	Stabilization	Cell survival		65
β-catenin	Ser246	ND	Stabilization and nuclear localization	Enhanced transcriptional activity		3, 17
Cyclin D1	Thr286	GSK-3β	Increased expression, stabilization, and nuclear localization	Cell cycle progression, enhanced proliferation		17, 18
Cyclin E	Ser384	CDK2	Regulation of protein stability	Cell cycle progression		3, 17, 53
c-JUN	Ser63, Ser73	JNK	Enhancement of transcriptional activity	Enhanced proliferation		9, 17
c-MYC	Thr58, Ser62	ERK, GSK-3β	Regulation of protein stability and transcriptional activity	Enhanced growth and metabolism		15, 53
ERα	Ser118, Ser294	MAPK, ERK, CDK2	Stabilization, enhanced DNA binding and transcriptional activity	Enhanced proliferation of ER+ BC cells, resistance to hormone therapy	Tamoxifen	17, 26
ERBB2/HER2	ND	ND	Stabilization	Enhanced proliferation of HER2+ BC	Rapamycin	10
FAK	Ser910	ERK	Promotes interaction with PTP-PEST	Enhanced HRAS-dependent migration, invasion and metastatic spread		62
FBXW7	Thr205	ND	Degradation	Enhanced cell proliferation		55
HIF-1α	Ser641, Ser643	ERK MAPK	Stabilization and promotion of transcriptional activity	Induction of angiogenesis and endocrine therapy resistance		34
MCL-1	Thr92, Thr163	ERK	Stabilization	Chemoresistance	Sorafenib	11
Mutant p53	Ser46, Ser315	AURKA/B	Enhances transcriptional activity and sequestration of p63	Enhanced mutant p53 pro-metastatic activities		13
STAT3	Ser727	ND	Promotes transcriptional activity	Promotion of EMT		60
NF-κB	Thr254	ND	Stabilization and nuclear localization	Enhanced transcriptional activity		3, 17
Notch1	Ser2122, Thr2133, Ser2137, Thr2512	ND	Processing of the membrane bound receptor, stabilization of the intracellular domain	Enhanced transcription, proliferation, CSCs self-renewal, tumorigenicity, chemoresistance	GSI (gamma secretase inhibitors)	12, 14
Notch4	ND	ND	Stabilization of the intracellular domain	Enhanced CSCs self-renewal and tumorigenicity		14
PML	Ser403, Ser505, Ser518, Ser527	ERK	Degradation	Enhanced cell proliferation		3, 17
pRB	Ser608, Ser612	CDK2/4/6	Hyper-phosphorylation and inactivation	Cell cycle progression, growth of Tamoxifen- resistant cells	PI3 Kinase Inhibitors	3, 17, 52
PTP-PEST	Ser571	ERK	Promotes interaction with FAK	HRAS-dependent migration, invasion and metastatic spread		62
RUNX3	Thr209, Thr212, Thr231, Ser214	ND	Degradation	Repression of RUNX3 transcriptional activity		3, 17
SMRT	Ser1241, Ser1469	CDK2	Degradation	Increased ER gene expression and cell proliferation		29, 31

Abbreviation: ND, not determined