Down-regulation of LHPP in cervical cancer influences cell proliferation, metastasis and apoptosis by modulating AKT

Zheng, Jiangli; Dai, Xue; Chen, Hailin; Fang, Chunli; Chen, Jian; Sun, Lichao

doi:10.1016/j.bbrc.2018.06.127

Cited by 62 publications

(72 citation statements)

References 32 publications

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“…Furthermore, the histidine phosphatase LHPP has been found to be associated with cancer. Here, we found that LHPP expression decreased in PaCa tissues and cells, indicating that LHPP was a potential tumor suppressor, which is consistent with the findings in melanoma and liver, cervical, and bladder cancers [9][10][11][12]. In our experiment, we also found that the degree of PaCa differentiation was negatively correlated with LHPP expression, and LHPP expression in PaCa with lymph node metastasis was significantly lower than in that without lymph node metastasis.…”

Section: Discussionsupporting

confidence: 90%

“…Recently, the anti-tumor effect of LHPP has been further demonstrated: LHPP is considered as a tumor suppressor gene of hepatocellular carcinoma by the PI3K/AKT signaling pathway, and its low expression leads to a decrease in patient survival rate [9]. In cervical cancer, it is also found that LHPP can promote apoptosis by increasing the expression of cleaved-PARP and cleaved-Casp3 protein [10]. As a new tumor suppressor, the anti-tumor effect of LHPP in melanoma and bladder cancer has been further confirmed [11,12].…”

Section: Introductionmentioning

confidence: 99%

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LHPP suppresses proliferation, migration, and invasion and promotes apoptosis in pancreatic cancer

Chen

Zhu

2020

Bioscience Reports

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Pancreatic cancer (PaCa) is a common malignant tumor of the digestive system with poor prognosis and no ideal treatment for inoperable patients, which is partly due to delayed diagnoses. It is recently reported that the protein histidine phosphatase LHPP is a tumor suppressor in hepatocellular carcinoma, cervical cancer, and bladder cancer. So far, there is no study on the expression level of LHPP in PaCa, and its mechanism of action on tumors is unclear. In this experiment, LHPP expression was lower in cancer tissues than that in normal pancreatic tissue, and clinicopathological results showed that LHPP expression was correlated with the degree of differentiation and lymphatic metastasis of pancreatic carcinoma. The biological characteristics of LHPP in PaCa cells were examined by the cell counting kit-8 assay, transwell assay, and monoclonal formation test. The inhibitory mechanism of LHPP in PaCa cells was determined using Western blotting and flow cytometry. The results showed that LHPP restrained PaCa cell proliferation, migration, and invasion. Increased LHPP expression promoted the apoptosis of PaCa cells through higher activation of cleaved-PARP and cleaved-Casp3 and lower activation of cIAP1. Importantly, the increase in LHPP enhanced PTEN expression and decreased the phosphorylated AKT level. Moreover, LHPP-induced apoptosis was diminished by SC79 (AKT activator) in PaCa cells. In conclusion, LHPP blocks proliferation, migration, and invasion and enhances apoptosis in PaCa cells through the PTEN/AKT signaling pathway.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

LHPP suppresses proliferation, migration, and invasion and promotes apoptosis in pancreatic cancer

Chen

Zhu

2020

Bioscience Reports

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“…It is lowly expressed in HCC specimens and its low expression correlates with the poor survival of HCC patients [5]. In another study, LHPP is also down-regulated in cervical cancer and silencing of LHPP promotes the progression of cervical cancer [8]. However, the role of LHPP in other cancer types, such as BC, is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

LHPP suppresses bladder cancer cell proliferation and growth via inactivating AKT/p65 signaling pathway

Zhang

Zhou

2019

Bioscience Reports

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Bladder cancer (BC) is one of the commonest malignancies in the urinary system. Recent evidences have shown that Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) serves as a tumor suppressor in hepatocellular carcinoma and cervical cancer. However, little is known about its function in BC. Here, we aimed to investigate the role of LHPP in BC. We found that LHPP was down-regulated in BC tissues and cells. Knockdown of LHPP promoted the proliferation and growth of BC cells T24 and 5637. Inverse results were observed in SW780 and BIU87 cells with ectopic LHPP expression. LHPP also repressed the glycolysis of BC cells. At the molecular level, LHPP silencing led to enhanced phosphorylation of both AKT and p65, as well as up-regulation of their downstream targets Bcl-2 and Cyclin D1. Inhibition of AKT by MK2206 blunted the increased phosphorylation of p65 caused by LHPP knockdown, suggesting that LHPP silencing activated p65 through AKT. Importantly, p65 inhibitor (caffeic acid phenethyl ester) exhibited larger suppressive effect on the proliferation of LHPP knockdown BC cells as compared with Ctrl cell. Our study demonstrates that LHPP suppresses BC cell growth via inactivating AKT/p65 signaling pathway.

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“…Sustained hepatic expression of LHPP in the HCC mouse model reduced tumor burden and prevented the loss of liver function and low expression of LHPP correlated with more advanced tumor and reduced overall survival in HCC patients [34]. Over-expressed LHPP reduced the tumor cell proliferation, migration and invasion possibly via blocking AKT activation and restraining p53 expression levels in cervical cancer cells [35]. So, LHPP is not only a protein histidine phosphatase but also a tumor suppressor.…”

Section: Discussionmentioning

confidence: 97%

The Roles of Epigenetic Regulators and Inflammasome in Hepatocellular Carcinoma Tumorigenesis in Patients with Alcoholic Steatohepatitis (ASH) vs Non-Alcoholic Steatohepatitis (NASH)

Jia¹

2019

COR

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As the fifth most common cancer and the second leading cause of cancer related deaths worldwide, hepatocellular carcinoma (HCC) is an aggressive tumor type with poor prognosis causing 250,000 to one million deaths annually. Alcoholic steatohepatitis (ASH) and non‐alcoholic steatohepatitis (NASH) are the two major growing risk factors and both may develop liver fibrosis or even HCC. However, compared with the rate of patients with ASH progressing to HCC annually, it is much lower in NASH patients. The present study is to clarify the protein expression of epigenetic regulators and Inflammasome components in the oncogenesis pathway between ASH and NASH. By using the immunofluorescence method and morphometrically quantitating the fluorescence intensity in liver biopsied specimens from NASH and ASH patients, we studied the protein expression within hepatocytes cytoplasm of candidate epigenetic regulators G9A and LHPP and inflammasome component ASC. Compared with the control group patients, the expression levels of all three proteins were upregulated in the ASH and NASH group of patients (p < 0.001 in all molecules). While compared with the ASH group of patients, only the expression levels of G9A were significantly lower in the NASH group of patients (p < 0.01). The other two molecules, LHPP and ASC did not change. These results are consistent with our previous work that there are significant differences of many molecules including epigenetic modulators and the inflammasome pathway in both NASH and ASH compared to the control group. Thus, we conclude that there are significantly different molecules and pathways involved during the pathogenesis of HCC development in NASH compared to ASH which may focus the light on developing prevention methods and targeted treatments in NASH and ASH patients. Support or Funding Information This study was funded by NIH/AAA grant # UO‐21898‐05. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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Down-regulation of LHPP in cervical cancer influences cell proliferation, metastasis and apoptosis by modulating AKT

Cited by 62 publications

References 32 publications

LHPP suppresses proliferation, migration, and invasion and promotes apoptosis in pancreatic cancer

LHPP suppresses proliferation, migration, and invasion and promotes apoptosis in pancreatic cancer

LHPP suppresses bladder cancer cell proliferation and growth via inactivating AKT/p65 signaling pathway

The Roles of Epigenetic Regulators and Inflammasome in Hepatocellular Carcinoma Tumorigenesis in Patients with Alcoholic Steatohepatitis (ASH) vs Non-Alcoholic Steatohepatitis (NASH)

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