E-cadherin inhibits tumor cell growth by suppressing PI3K/Akt signaling via β-catenin-Egr1-mediated PTEN expression

Lau, M-T; Klausen, Christian; Leung, Peter C.K.

doi:10.1038/onc.2011.6

Cited by 118 publications

(82 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The present study hypothesized that UHRF1 may inhibit the expression of Rb1 and thereby suppress the expression of E-cadherin. E-cadherin is known to suppress the invasion of cancer cells (25). Therefore, the UHRF1-mediated promotion of invasion may be the result of E-cadherin inhibition.…”

Section: Uhrf1 Suppresses the Expression Of E-cadherin And Promotes Ementioning

confidence: 99%

UHRF1 promotes human osteosarcoma cell invasion by downregulating the expression of E-cadherin in an Rb1-dependent manner

Liu

Qiao

Wang

et al. 2015

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Ubiquitin-like with plant homeodomain (PHD) and RING-finger domain 1 (UHRF1) maintains methylation patterns following DNA replication and is expressed at high levels in various types of human cancer. UHRF1 has been identified as a novel oncogene involved in the pathogenesis of hepatocellular carcinoma. Previous studies have demonstrated that inhibition of the expression of UHRF1 suppresses the proliferation of cancer cells. However, the role of UHRF1 in human osteosarcoma has not been investigated. The present study examined the expression levels of UHRF1 and retinoblastoma 1 (Rb1) in human osteosarcoma cell lines by western blot analysis. Stable overexpression of UHRF1 or knockdown of Rb1 was achieved by lentiviral transfection. Subsequently, a Cell Counting Kit-8 assay and a cell invasion assay were performed to detect the biological functions of UHRF1 in vitro. The results of the present study demonstrated that UHRF1 promoted the proliferation of human osteosarcoma cells. The present study also reported that UHRF1 was able to enhance the invasion of osteosarcoma cells in a retinoblastoma 1 (Rb1)-dependent manner. UHRF1 promoted invasion in Rb1-positive osteosarcoma cells, but not in Saos-2 cells with homozygous loss of Rb1. Similarly, knockdown of Rb1 in Rb1-positive osteosarcoma cells enhanced levels of invasion and eliminated the regulation of invasion by UHRF1. UHRF1 was found to inhibit the mRNA and protein expression levels of Rb1. Furthermore, deletion of Rb1 was found to suppress the expression of E-cadherin and promote epithelial-to-mesenchymal transition (EMT). In addition, the overexpression of UHRF1 inhibited the expression of E-cadherin and promoted EMT via the suppression of Rb1. These data demonstrated that UHRF1 promotes osteosarcoma cell invasion by downregulating the expression of E-cadherin and increasing EMT in an Rb1-dependent manner.

show abstract

Section: Uhrf1 Suppresses the Expression Of E-cadherin And Promotes Ementioning

confidence: 99%

UHRF1 promotes human osteosarcoma cell invasion by downregulating the expression of E-cadherin in an Rb1-dependent manner

Liu

Qiao

Wang

et al. 2015

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…The anchorage-independent growth of cancer cells is one of the hallmarks of malignant phenotypes and promoted by loss of E-cadherin (18). Soft agar assays revealed that PLCδ1 reduced the anchorage-independent cell growth of SW620 cells (Fig.…”

Section: Plcδ1 Suppresses Anchorage-independent Cell Growth Andmentioning

confidence: 99%

Phospholipase Cδ1 induces E-cadherin expression and suppresses malignancy in colorectal cancer cells

Satow

Hirano

Batori

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

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 Cδ1 (PLCδ1) expression and KRAS mutation status in CRC. However, both the roles and the regulatory mechanisms of PLCδ1 in CRC are not known. Here, we found that the expression of PLCδ1, 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 PLCδ1 in CRC cell lines that harbor an activating KRAS mutation. Ectopic expression of PLCδ1 in CRC cells induced the expression of E-cadherin, whereas knockdown of PLCδ1 repressed the expression of E-cadherin. Moreover, the overexpression of PLCδ1 suppressed the expression of several mesenchymal genes and reduced cell motility, invasiveness, and in vivo tumorigenicity of SW620 CRC cells. We also showed that PLCδ1 expression is repressed by the KRAS/mitogen-activated protein kinase kinase (MEK) pathway. Furthermore, PLCδ1 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 PLCδ1. These data indicate that PLCδ1 has tumor-suppressive functions in CRC through E-cadherin induction and KRAS/MEK/ERK signal attenuation.phospholipase C delta 1 | epithelial-to-mesenchymal transition | tumor suppressor C olorectal cancer (CRC) is one of the most common cancers and causes of cancer-related deaths worldwide. Although CRC patients with unresectable tumors and metastasis have been treated with chemotherapy, recent advances in molecular research about CRC have resulted in the development of molecular targeted therapies, such as cetuximab and panitumumab. Chemotherapy combined with these targeted therapies improves the prognosis of CRC patients with unresectable tumors to some extent (1, 2). However, some CRC patients with activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are unable to benefit from such drugs, because both cetuximab and panitumumab are epidermal growth factor (EGF) receptor-targeting agents and mutant KRAS constitutively activates the downstream signaling of EGF receptor (3). A more vigorous study using KRAS-mutant CRC is needed to identify novel molecular targets for drugs that will improve the prognosis of CRC patients with unresectable tumors, especially those with KRAS mutations.Mutations in KRAS are found in about 40% of CRC patients. Constitutively active KRAS mutations lead to the hyperactivation of mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) [mitogen-activated protein kinase (MAPK)] signaling and/or phosphatidylinositol-3 kinase (PI3K) pathways (4). Activation of MEK/ERK (MAPK) signaling results in increased phosphorylation...

show abstract

“…Although research findings have been accumulating to reveal the ubiquitous expression of E-cadherin and its exact role in ovarian cancers, there are still many opposite opinions [20] as well as lots of unsolved questions. For instance, Sawada reported that loss of E-cadherin promotes ovarian cancer cells metastasis via alpha 5-integrin [31] .…”

Section: Wwwchinapharcom Dong Ll Et Almentioning

confidence: 99%

“…However, the mechanism that how E-cadherin plays its role during the development of ovarian cancer still remains unclear. Moreover, contradictory data have suggested that E-cadherin could inhibit tumor cell growth by suppressing phosphatidylinositol 3-kinase (PI3K)/ Akt signaling in ovarian cancer cells [20] . In the present study, to determine the possible functions of E-cadherin in ovarian cancer cells, we knocked down the CDH1 gene expression via RNA interference (RNAi) in the SKOV-3 ovarian cancer cells.…”

Section: Introductionmentioning

confidence: 99%

E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway

Liu

et al. 2012

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: E-cadherin is unusually highly expressed in most ovarian cancers. This study was designed to investigate the roles of E-cadherin in the carcinogenesis and progression of ovarian cancers. Methods: Human ovarian adenocarcinoma cell line SKOV-3 was examined. E-cadherin gene CDH1 in SKOV-3 cells was knocked down via RNA interference (RNAi), and the resultant variation of biological behavior was observed using CCK-8 and colony formation experiment. E-cadherin-mediated Ca 2+ -dependent cell-cell adhesion was used to study the mechanisms underlying the effects of E-cadherin on the proliferation and survival of SKOV-3 cells. The expression levels of E-cadherin, extracellular signal-related kinase (ERK), phosphorylated ERK (P-ERK) were measured using Western blot assays. Results: Transfection with CDH1-siRNA for 24-96 h significantly suppressed the growth and proliferation of SKOV-3 cells. E-cadherinmediated calcium-dependent cell-cell adhesion of SKOV-3 cells resulted in a rapid increase of P-ERK, but did not modify the expression of ERK protein. The phosphorylation of ERK in the cells was blocked by pretreatment with the MEK1 specific inhibitor PD98059 (50 μmol/L), but not by the PI3K inhibitor wortmannin (1 μmol/L) or PKA inhibitor H89 (10 μmol/L).Conclusion: E-cadherin may function as a tumor proliferation enhancer via activating the MEK/ERK pathway in development of ovarian epithelial cancers.

show abstract

E-cadherin inhibits tumor cell growth by suppressing PI3K/Akt signaling via β-catenin-Egr1-mediated PTEN expression

Cited by 118 publications

References 56 publications

UHRF1 promotes human osteosarcoma cell invasion by downregulating the expression of E-cadherin in an Rb1-dependent manner

UHRF1 promotes human osteosarcoma cell invasion by downregulating the expression of E-cadherin in an Rb1-dependent manner

Phospholipase Cδ1 induces E-cadherin expression and suppresses malignancy in colorectal cancer cells

E-cadherin promotes proliferation of human ovarian cancer cells in vitro via activating MEK/ERK pathway

Contact Info

Product

Resources

About