Abstract LB-B21: BI-69A11 inhibits Epithelial to Mesenchymal Transition exploiting β-catenin pathway in colon carcinoma

Abstract

Abstract EMT is a potential biological phenomena required for metastatic dissemination. Although targeting EMT for therapeutic implication has been gaining interest to the scientific community, only few molecules have succeeded to employ their anti-metastatic effect so far. BI-69A11 has been earlier proved for its anti-tumor activity in prostate and colon carcinoma. This study aims to elucidate the biological consequence of BI-69A11 on EMT in colon carcinoma in vitro and in vivo. Our findings showed that BI-69A11 increased epithelial signature marker E-cadherin and reciprocally decreased the mesenchymal markers snail, slug and vimentin. Moreover, cellular migration, invasion and adhesion were potentially hampered by BI-69A11 through β-catenin dependent pathway. The underlying molecular mechanism behind BI-69A11 induced inhibition of EMT includes suppression of nuclear transport of β-catenin, diminished phosphorylation of β-catenin accompanied with enhanced E-cadherin- β-catenin complex formation at the membrane. Moreover, BI-69A11 controlled the transcriptional activity and reversed nuclear translocation by decrease in the phosphorylation at ser552 and ser45/Thr41 residue. The growing interaction between E-cadherin and β-catenin complex also promoted the E-cadherin transcription leading to the reversal of EMT. BI-69A11 caused increasing accumulation of vinculin in the membrane that in turn strengthened the focal adhesion junction leading to the inhibition of metastasis. Overall, these evidences present a thoughtful insight towards underlying molecular mechanism of BI-69A11 induced reversal of EMT in colorecteal carcinoma in vitro and in vivo. Citation Format: Ipsita Pal, Mahitosh Mandal. BI-69A11 inhibits Epithelial to Mesenchymal Transition exploiting β-catenin pathway in colon carcinoma. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-B21.