Page 12 - D. Cancer biology

[D. Cancer biology-7]

Inhibition of Phospholipase D1 attenuates colorectal cancer

growth hyperactivated by Wnt and PI3K signaling via

upregulation of ICAT

Won Chan Hwang¹, Venu Venkatarame Gowda Saralamma¹, Ju Won Kim¹, MinJu Kang¹, RaeHee Kang¹,

Hyun Ji Lee¹, Do Sik Min¹

¹College of pharmacy, Yonsei University, Incheon 21983, Korea

Dysregulated expression of PLD1 has emerged as a hallmark feature of colorectal cancer, which remains a major

cause of mortality worldwide. Aberrant activation of Wnt/β-catenin signaling is a critical event in the development
of colorectal cancer. Here, we investigated molecular crosstalk between the Wnt/β-catenin and PI3K/Akt pathways

via inhibitor of β-catenin and T-cell factor (ICAT), a negative regulator of Wnt/β-catenin signaling. We also explored
the effect of PLD1 inhibition on growth of colorectal cancer hyperactivated by Wnt/β-catenin and PI3K/Akt signaling.

Our results suggest that PLD1 linked to ICAT mediates molecular crosstalk between the Wnt/β-catenin and PI3K/Akt
pathways and thus could be proposed as a novel colorectal cancer prognostic biomarker. These results may assist

in the clinical development of a PLD1 inhibitor for treatment of colorectal cancer patients carrying APC and PI3KCA
mutations. PLD1, a nodal modifier, acts as a potential therapeutic target for the treatment of colorectal cancer

hyperactivated by the Wnt/β-catenin and PI3K/Akt signaling pathways.