Peptidyl-prolyl isomerase Pin1-mediated abrogation of APC-β-catenin interaction in squamous cell carcinoma of cervix.
OBJECTIVE
The present study was aimed to investigate the importance of Pin1 expression in Squamous Cell Carcinoma (SCC) of cervix and to assess its level with β-catenin and APC to understand the possible involvement of Pin1 in the regulation of these proteins and subsequent activation of Wnt/β-catenin signaling.


METHODS
Expression of Pin1, β-catenin and APC was examined in 153 SCC patients by immunohistochemistry and revalidated by western blotting.


RESULTS
Of the 153 SCC analyzed, Pin1 was overexpressed in 73 (47.71%) cases. Loss of membranous β-catenin was noticed in 117 (76.47%) SCCs, whereas 66/153 (43.13%) and 93/153 (60.78%) cases showed its distinct cytoplasmic as well as nuclear accumulation respectively. Down regulation/loss of APC was observed in 69 (45.09%) cases, suggesting the activation of Wnt/β-catenin pathway in SCCs. Pin1 showed the significant association with nuclear β-catenin (r=.349, p<0.0001) and cytoplasmic loss of APC (r=-.287, p<0.0001). Both Pin1 as well as nuclear β-catenin were found to be associated with tumor stage (p=0.004, p=0.031) and tumor size (p=0.022, p=0.003). The Pin1 overexpression showed the significant association with disease free survival (p=0.002) but not with overall survival (p=0.421) of SCC patients.


CONCLUSIONS
Current results explore the expressional relationship between Pin1, β-catenin and APC suggesting that Pin1 regulates the activation of Wnt/β-catenin pathway in SCCs via modulating the interaction between β-catenin and APC. Furthermore, the significant association of Pin1 and β-catenin with tumor variables underscores the clinical utility of these proteins in cervical cancer.
Department of Anatomy, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India; gayatrirathvmmc@gmail.com, poonamrnirmal@gmail.com.
Poonam
P
Jawanjal
Sudha
S
Salhan
Indrani
I
Dhawan
Richa
R
Tripathi
Gayatri
G
Rath
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D011485:Protein Binding; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism*
C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D051176:beta Catenin; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase