5337

PLD1

-;phospholipase D1, phosphatidylcholine-specific;PLD1;phospholipase D1, phosphatidylcholine-specific

choline phosphatase 1|phosphatidylcholine-hydrolyzing phospholipase D1|phospholipase D1

3q26

protein-coding

Colorectal cancer (CRC) is one of the most common causes of cancer-related deaths worldwide, and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in CRC predict the ineffectiveness of EGF receptor-targeted therapy. Previous transcriptional microarray analysis suggests the association between phospholipase Cdelta1 (PLCdelta1) expression and KRAS mutation status in CRC. However, both the roles and the regulatory mechanisms of PLCdelta1 in CRC are not known. Here, we found that the expression of PLCdelta1, one of the most basal PLCs, is down-regulated in CRC specimens compared with normal colon epithelium by immunohistochemistry. Furthermore, we examined the roles of PLCdelta1 in CRC cell lines that harbor an activating KRAS mutation. Ectopic expression of PLCdelta1 in CRC cells induced the expression of E-cadherin, whereas knockdown of PLCdelta1 repressed the expression of E-cadherin. Moreover, the overexpression of PLCdelta1 suppressed the expression of several mesenchymal genes and reduced cell motility, invasiveness, and in vivo tumorigenicity of SW620 CRC cells. We also showed that PLCdelta1 expression is repressed by the KRAS/mitogen-activated protein kinase kinase (MEK) pathway. Furthermore, PLCdelta1 suppressed the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 through E-cadherin induction in CRC cells, suggesting the presence of a negative regulatory loop between KRAS/MEK/ERK signaling and PLCdelta1. These data indicate that PLCdelta1 has tumor-suppressive functions in CRC through E-cadherin induction and KRAS/MEK/ERK signal attenuation.