PKCε inhibits isolation and stemness of side population cells via the suppression of ABCB1 transporter and PI3K/Akt, MAPK/ERK signaling in renal cell carcinoma cell line 769P

Huang, Bin; Fu, Shun; Fan, Wen; Wang, Zhong Hua; Chen, Ze Bin; Guo, Sheng; Chen, Jun Xing; Qiu, Shaopeng

doi:10.1016/j.canlet.2016.03.041

Cited by 49 publications

(39 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Emerging evidences suggested that PRKCE plays oncogenic role through increasing survival protein levels, which sustained cancer stem cell development. 17 Our study reinforced the oncogenic role of PRKCE in increasing gemcitabine resistance and its correlation with a poor prognosis in GBC tumors. The inverse relationship between miR-218-5p and PRKCE was then confirmed in GBC tissues.…”

Section: Discussionsupporting

confidence: 75%

“…27 Consistent with the previous report in renal carcinoma cells that reduce the expression of PRKCE lowered MDR1 /P-gp, which affects the cancer stem cell potential of sorted side population cells and suppresses proliferation potential, resistance to chemotherapeutics and in vivo tumor formation ability. 17 Our identification of the regulatory role of miR-218-5p- PRKCE - MDR1 axis in GBC cells further confirmed its importance.…”

Section: Discussionsupporting

confidence: 65%

“…15 PRKCE, a member of protein kinase C (PKC) family, is a serine- and threonine-specific protein kinase that actively participate in promoting drug resistance through phosphorylating a variety of protein targets, such as P-gp, ATF2, PI3K, Stat3, and Erk. 16, 17 …”

mentioning

confidence: 99%

See 2 more Smart Citations

miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer

Wang

Zhan

et al. 2017

Cell Death Dis

View full text Add to dashboard Cite

Gallbladder cancer (GBC) is one of the most common malignancy of the biliary tract characterized by its high chemoresistant tendency. Although great progresses have been made in recent decades for treating many cancers with anticancer drugs, effective therapeutics methods for anti-GBC are still lacking. Therefore, investigations into identifying the mechanisms underlying the drug resistance of GBC are greatly needed. In this study, we show that miR-218-5p plays a critical role in gemcitabine resistance of GBC. miR-218-5p levels were significantly lower in GBC than adjacent non-cancer tissues, and which were also associated with patient prognosis. While miR-218-5p overexpression abrogated gemcitabine resistance of GBC cells, silencing of which exhibited the opposite effects. Via six microRNA targets prediction algorithms, we found that PRKCE is a potential target of miR-218-5p. Moreover, miR-218-5p overexpression repressed the luciferase activity of reporter constructs containing 3′-UTR of PRKCE and also reduced PRKCE expression. Further studies revealed that miR-218-5p promotes sensitivity of gemcitabine by abolishing PRKCE-induced upregulation of MDR1/P-gp. Taken together, our results imply that an intimate correlation between miR-218-5p and PRKCE/MDR1 axis abnormal expression is a key determinant of gemcitabine tolerance, and suggest a novel miR-218-5p-based clinical intervention target for GBC patients.

show abstract

Section: Discussionsupporting

confidence: 75%

Section: Discussionsupporting

confidence: 65%

See 1 more Smart Citation

miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer

Wang

Zhan

et al. 2017

Cell Death Dis

View full text Add to dashboard Cite

show abstract

“…Fang et al suggested that the ERK1/2 signaling pathway mediates the regulation of cell cycle-related proteins, effectively inhibits cell proliferation, and also causes G1 phase arrest in RCC cell lines [123]. Protein kinase C epsilon (PKCε) plays as an important mediator in cancer stem cell pathogenesis of renal cell cancer by regulating the phosphorylation of ERK1/2 in RCC 769P side population cell line [124]. Xu et al suggested that the anti-tumor activities of acyldepsipeptides are dependent on the down-regulated expressions of cyclin D1, CDK4, and PCNA, along with the decreased expression of phosphorylated ERK1/2 in renal 786-O and 769-P cells [125].…”

Section: Erk1/2mentioning

confidence: 99%

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

Luo

Shi

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Tissue hypoxia/ischemia is a pathological feature of many human disorders including stroke, myocardial infarction, hypoxic/ischemic nephropathy, as well as cancer. In the kidney, the combination of limited oxygen supply to the tissues and high oxygen demand is considered the main reason for the susceptibility of the kidney to hypoxic/ischemic injury. In recent years, increasing evidence has indicated that a reduction in renal oxygen tension/blood supply plays an important role in acute kidney injury, chronic kidney disease, and renal tumorigenesis. However, the underlying signaling mechanisms, whereby hypoxia alters cellular behaviors, remain poorly understood. Mitogen-activated protein kinases (MAPKs) are key signal-transducing enzymes activated by a wide range of extracellular stimuli, including hypoxia/ischemia. There are four major family members of MAPKs: the extracellular signal-regulated kinases-1 and -2 (ERK1/2), the c-Jun N-terminal kinases (JNK), p38 MAPKs, and extracellular signal-regulated kinase-5 (ERK5/BMK1). Recent studies, including ours, suggest that these MAPKs are differentially involved in renal responses to hypoxic/ischemic stress. This review will discuss their changes in hypoxic/ischemic pathophysiology with acute kidney injury, chronic kidney diseases and renal carcinoma.

show abstract

“…Multiple signaling pathways have been shown to be involved in the regulation of EMT and CSC transition , and there are many common regulation mechanisms between EMT and CSC. For instance, extracellular signal‐regulated kinase (ERK) signaling has been shown to be involved in the regulation of both stemness and EMT in several cancers. Wnt/β‐catenin pathway can promote the expression of surface markers of liver cancer and the promotion of liver CSC activation and is involved in EMT of HCC .…”

mentioning

confidence: 99%

Mammalian‐enabled (MENA) protein enhances oncogenic potential and cancer stem cell‐like phenotype in hepatocellular carcinoma cells

Huang

Luo

et al. 2017

FEBS Open Bio

View full text Add to dashboard Cite

Mammalian‐enabled ( MENA ) protein is an actin‐regulatory protein that influences cell motility and adhesion. It is known to play a role in tumorigenicity of hepatocellular carcinoma ( HCC ) but the underlying molecular mechanism remains unknown. This study aimed to investigate the oncogenic potential of MENA and its capacity to regulate cancer stem cell ( CSC )‐like phenotypes in HCC cells. Real‐time‐ PCR and western blot were used to assess mRNA and protein levels of target genes in human HCC tissue specimens and HCC cell lines, respectively. Stable MENA ‐overexpressing HCC cells were generated from HCC cell lines. Transwell cell migration and colony formation assays were employed to evaluate tumorigenicity. Ectopic expression of MENA significantly enhanced cell migration and colony‐forming ability in HCC cells. Overexpression of MENA upregulated several hepatic progenitor/stem cell markers in HCC cells. A high MENA protein level was associated with high mRNA levels of MENA , CD 133, cytokeratin 19 ( CK 19), and epithelial cell adhesion molecule (Ep CAM ) in human HCC tissues. Overexpression of MENA enhanced epithelial‐to‐mesenchymal transition ( EMT ) markers, extracellular signal‐regulated kinases ( ERK ) phosphorylation, and the level of β‐catenin in HCC cells. This study demonstrated that overexpression of MENA in HCC cells promoted stem cell markers, EMT markers, and tumorigenicity. These effects may involve, at least partially, the ERK and β‐catenin signaling pathways.

show abstract

PKCε inhibits isolation and stemness of side population cells via the suppression of ABCB1 transporter and PI3K/Akt, MAPK/ERK signaling in renal cell carcinoma cell line 769P

Cited by 49 publications

References 36 publications

miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer

miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer

Mitogen-Activated Protein Kinases and Hypoxic/Ischemic Nephropathy

Mammalian‐enabled (MENA) protein enhances oncogenic potential and cancer stem cell‐like phenotype in hepatocellular carcinoma cells

Contact Info

Product

Resources

About