Growth of the pancreatic cancer cell line PANC-1 is inhibited by protein phosphatase 2A inhibitors through overactivation of the c-Jun N-terminal kinase pathway

Li, Wei; Zheng, Cuifang; Gong, Fei‐Ran; Zong, Yang; Chen, Kai; Li, Daoming; Yin, Hong; Duan, Weiming; Miao, Yi; Tao, Min; Han, Xiao; Xu, Zekuan

doi:10.1016/j.ejca.2011.08.014

Cited by 39 publications

(59 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, PP2Ac overexpression induced apoptosis and repressed pancreatic cancer cell growth. 6,11 These results suggested that PP2A plays a tumor suppressor role and could be a potential target for cancer treatment.…”

Section: Introductionmentioning

confidence: 88%

“…A third regulatory B subunit is associated with this core structure. 6 PP2Ac has a and b isoforms, whose primary sequences share 97% identity. 7 Defects in the expression of PP2A components have been linked to cancer.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 PP2A modulates several signaling cascades, including that of c-Jun N-terminal kinase (JNK), extracellular signal-related kinase (ERK), p38, Akt and protein kinase C (PKC) among others, most of which can accelerate growth. 6 The core PP2A enzyme consists of a catalytic subunit (PP2Ac) and a regulatory subunit termed the A subunit. A third regulatory B subunit is associated with this core structure.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac

et al. 2016

Self Cite

View full text Add to dashboard Cite

Previous studies have indicated that inflammatory stimulation represses protein phosphatase 2A (PP2A), a well-known tumor suppressor. However, whether PP2A repression participates in pancreatic cancer progression has not been verified. We used lipopolysaccharide (LPS) and macrophage-conditioned medium (MCM) to establish in vitro inflammation models, and investigated whether inflammatory stimuli affect pancreatic cancer cell growth and invasion PP2A catalytic subunit (PP2Ac)-dependently. Via nude mouse models of orthotopic tumor xenografts and dibutyltin dichloride (DBTC)-induced chronic pancreatitis, we evaluated the effect of an inflammatory microenvironment on PP2Ac expression in vivo. We cloned the PP2Aca and PP2Acb isoform promoters to investigate the PP2Ac transcriptional regulation mechanisms. MCM accelerated pancreatic cancer cell growth; MCM and LPS promoted cell invasion. DBTC promoted xenograft growth and metastasis, induced tumor-associated macrophage infiltration, promoted angiogenesis, activated the nuclear factor-kB (NF-kB) pathway, and repressed PP2Ac expression. In vitro, LPS and MCM downregulated PP2Ac mRNA and protein. PP2Aca overexpression attenuated JNK, ERK, PKC, and IKK phosphorylation, and impaired LPS/MCM-stimulated cell invasion and MCM-promoted cell growth. LPS and MCM activated the NF-kB pathway in vitro. LPS and MCM induced IKK and IkB phosphorylation, leading to p65/RelA nuclear translocation and transcriptional activation. Overexpression of the dominant negative forms of IKKa attenuated LPS and MCM downregulation of PP2Ac, suggesting inflammatory stimuli repress PP2Ac expression NF-kB pathway-dependently. Luciferase reporter gene assay verified that LPS and MCM downregulated PP2Ac transcription through an NF-kB-dependent pathway. Our study presents a new mechanism in inflammation-driven cancer progression through NF-kB pathway-dependent PP2Ac repression.

show abstract

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…133,134 Inhibition of PP2A with cantharidins has been previously shown to suppress growth of pancreatic cancer cells in vitro through sustained activation of the NF-kB pathway, hyperactivation of the c-Jun/JNK pathway, and inhibition of the Wnt/B-catenin pathway. 11,135,136 Based on these findings, PP2A inhibition was studied in pancreatic cancer cells for its potential as a radiosensitizing agent. Via high-throughput siRNA library screen in human pancreatic cancer cells, Wei et al identified depletion of the subunit PPP2R1A as a significant sensitizer to gemcitabine and radiation.…”

Section: Pancreatic Cancermentioning

confidence: 99%

LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential

Zhang

et al. 2015

Cancer Biology & Therapy

103

View full text Add to dashboard Cite

“…[48][49][50] Cantharidin, another PP2A inhibitor, suppresses the migration and growth of pancreatic and breast cancer cells. 48,[51][52][53] We also previously reported that OA induced apoptosis in several types of cell line including osteosarcoma cells through NF-κB and PKR pathways. 17,18 Furthermore, genistein attenuates the proliferative rate and invasive potential of LM8 cells.…”

Section: Discussionmentioning

confidence: 99%

Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells

Yang

Okamura

Morimoto

et al. 2016

Laboratory Investigation

View full text Add to dashboard Cite

Osteosarcoma is the most frequent primary bone tumor. Serine/threonine protein phosphatase 2A (PP2A) participates in regulating many important physiological processes, such as cell cycle, growth, apoptosis, and signal transduction. In this study, we examined the expression and function of PP2A Cα in osteosarcoma cells. PP2A Cα expression was expected to be higher in malignant osteosarcoma tissues. PP2A Cα expression level and PP2A activity was higher in malignant osteosarcoma LM8 cells compared with that in primary osteoblasts and in the osteoblast-like cell line MC3T3-E1. Okadaic acid, an inhibitor of PP2A, reduced cell viability and induced apoptosis in LM8 cells. PP2A Cα-knockdown LM8 cells (shPP2A) exhibited less striking filopodial and lamellipodial structures than that in original LM8 cells. Focal adhesion kinase phosphorylation and NF-κB activity decreased in shPP2A-treated cells. Sensitivity to serum deprivation-induced apoptosis increased in shPP2A-treated cells, accompanied by a lower expression level of anti-apoptotic BCL-2 in these cells. Reduction of PP2A Cα resulted in a decrease in the migration ability of LM8 cells in vitro. Reduction in PP2A Cα levels in vivo suppressed proliferation and metastasis in LM8 cells. PP2A Cα expression was also higher in human osteosarcoma MG63 and SaOS-2 cells than that in primary osteoblasts and MC3T3-E1 cells, and reduction in PP2A Cα levels suppressed the cell proliferation rate and migration ability of MG63 cells. These results indicate that PP2A Cα has a critical role in the proliferation and metastasis of osteosarcoma cells; therefore, its inhibition could potentially suppress the malignancy of osteosarcoma cells.

show abstract

Growth of the pancreatic cancer cell line PANC-1 is inhibited by protein phosphatase 2A inhibitors through overactivation of the c-Jun N-terminal kinase pathway

Cited by 39 publications

References 34 publications

Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac

Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac

LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential

Protein phosphatase 2A Cα regulates proliferation, migration, and metastasis of osteosarcoma cells

Contact Info

Product

Resources

About