The phosphoinositide hydrolase phospholipase C delta1 inhibits epithelial‐mesenchymal transition and is silenced in colorectal cancer

Abstract

In this study, we found that the phospholipase C delta1 (PLCD1) protein expression is reduced in colorectal tumor tissues compared with paired surgical margin tissues. PLCD1‐promoted CpG methylation was detected in 29/64 (45%) primary colorectal tumors, but not in nontumor tissues. The PLCD1 RNA expression was also reduced in three out of six cell lines, due to PLCD1 methylation. The ectopic expression of PLCD1 resulted in inhibited proliferation and attenuated migration of colorectal tumor cells, yet promoted colorectal tumor cell apoptosis in vitro. We also observed that PLCD1 suppressed proliferation and promoted apoptosis in vivo. In addition, PLCD1 induced G1/S phase cell cycle arrest. Furthermore, we found that PLCD1 led to the downregulation of several factors downstream of β‐catenin, including c‐Myc and cyclin D1, which are generally known to be promoters of tumorigenesis. This downregulation was caused by an upregulation of E‐cadherin in colorectal tumor cells. Our findings provide insights into the role of PLCD1 as a tumor suppressor gene in colorectal cancer (CRC), and demonstrate that it plays significant roles in proliferation, migration, invasion, cell cycle progression, and epithelial‐mesenchymal transition. On the basis of these results, tumor‐specific methylation of PLCD1 could be used as a novel biomarker for early detection and prognostic prediction in CRC.

The tumor suppressor Zinc finger protein 471 suppresses breast cancer growth and metastasis through inhibiting AKT and Wnt/β-catenin signaling

“…Cellular proteins were extracted and western blotting was performed as previously described [ 26 , 29 , 30 ]. Protein lysates (40 μg) were separated by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and transferred onto polyvinylidene fluoride membranes.…”

Origin recognition complex 1 regulates phospholipase Cδ1 to inhibit cell proliferation, migration and epithelial‑mesenchymal transition in lung adenocarcinoma

“…A previous study has also demonstrated low expression of PLCD1 in colorectal cancer cells and indicated that restoring PLCD1 expression inhibited colorectal cancer cell proliferation and induced apoptosis; furthermore, restoration of PLCD1 inhibited cell proliferation, metastasis and tumorigenicity in colorectal cancer ( 21 ). In esophageal squamous carcinoma cells, PLCD1 was indicated to inhibit cell proliferation, invasion and migration by suppressing the Wnt/β-catenin signaling pathway ( 22 ).…”

Differentially methylated CpG sites associated with the high-risk group of prostate cancer

“…According to literature, cancer-associated hypermethylation was previously shown for the STK33 [34][35][36], IQSEC1 [37], and PLCD1 [38][39][40][41][42][43] genes, however, a decrease in the expression was observed only for IQSEC1 [37] and PLCD1 [38][39][40][41][42][43] (Table 4). CSRNP1 and C6orf141 were found to be downregulated with no studied methylation status.…”

“…Notably, aberrant methylation of the STK33, and PLCD1 genes was observed in other cancers. In particular, often promoter hypermethylation of the PLCD1 gene was shown to be associated with its downregulation in breast [38], gastric [39], and colorectal cancers [40], as well as chronic myeloid leukemia [41]. In colorectal cancer, PLCD1 promoter hypermethylation and its decreased expression were correlated with tumor progression [42].…”