Transcription factor Sp1 is upregulated by PKCι to drive the expression of YAP1 during pancreatic carcinogenesis.
Carcinogenesis
; 42(3): 344-356, 2021 04 17.
Article
in En
| MEDLINE
| ID: mdl-33146712
ABSTRACT
Recently, we identified that the atypical protein kinase C isoform ι (PKCι) enhances the expression of Yes-associated protein 1 (YAP1) to promote the tumorigenesis of pancreatic adenocarcinoma harboring mutant KRAS (mu-KRAS). To advance our understanding about underlying mechanisms, we analyze the transcription of YAP1 in pancreatic cancer cells and reveal that transcription factor specificity protein 1 (Sp1) is upregulated by PKCι and subsequently binds to multiple sites in YAP1 promoter to drive the transactivation of YAP1 in pancreatic cancer cells carrying mu-KRAS. The bioinformatics analysis further substantiates that the expression of PKCι, Sp1 and YAP1 is correlated and associated with the stages and prognosis of pancreatic tumors. Moreover, our apoptotic detection data demonstrate that combination of PKCι and Sp1 inhibitors at subtoxic doses displays synergistic effects on inducing apoptosis and reversing the immunosuppression of pancreatic cancer cells, establishing the combination of PKCι and Sp1 inhibitors as a promising novel therapeutic approach, or an adjuvant strategy to potentiate the antitumor effects of other immunotherapeutic agents in pancreatic cancer treatment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Transcription Factors
/
Protein Kinase C
/
Antineoplastic Combined Chemotherapy Protocols
/
Sp1 Transcription Factor
/
Adaptor Proteins, Signal Transducing
/
Isoenzymes
Type of study:
Prognostic_studies
Language:
En
Journal:
Carcinogenesis
Year:
2021
Type:
Article