Clinical significance of clusterin expression in pancreatic adenocarcinoma

Jin, Junshuo; Kim, Joon Mee; Hur, Yoon Seok; Cho, Won Pyo; Lee, Keon-Young; Ahn, Seung-Ik; Hong, Kwang Pyo; Park, Insun

doi:10.1186/1477-7819-10-146

Cited by 9 publications

(8 citation statements)

References 30 publications

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“…APOJ expression was significantly upregulated in RCC tissues and could be an independent prognostic factor . APOJ overexpression in gastric cancer was associated with tumor progression and metastasis and in pancreatic carcinoma with lymph node metastasis . However, cytoplasmic APOJ expression was related to longer survival in NSCLC patients after surgery …”

Section: Apolipoproteins and Cancermentioning

confidence: 98%

Apolipoproteins and cancer

et al. 2019

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The role of apolipoproteins in cardiovascular disease has been well investigated, but their participation in cancer has only been explored in a few published studies which showed a close link with certain kinds of cancer. In this review, we focused on the function of different kinds of apolipoproteins in cancers, autophagy, oxidative stress, and drug resistance. The potential application of apolipoproteins as biomarkers for cancer diagnosis and prognosis was highlighted, together with an investigation of their potential as drug targets for cancer treatment. Many important roles of apolipoproteins and their mechanisms in cancers were reviewed in detail and future perspectives of apolipoprotein research were discussed.

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Section: Apolipoproteins and Cancermentioning

confidence: 98%

Apolipoproteins and cancer

et al. 2019

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“…A pioneering work by Scaltriti et al (2004) suggested that CLU counteracts cell migration and invasion. Conversely, more recent works from different laboratories indicate that it enhances cell migration in several cell models (Jin et al, 2012;Niu et al, 2012). Although there is some evidence that in macrophages, CLU promotes chemotactic migration through upregulation of matrix metalloproteinase-9 and NF-kB activation downstream of AKT and Erk1/2 (Shim et al, 2011;Shim, Kang, Choi, Park, & Min, 2012), hitherto its molecular mechanisms in prostate cells have remained elusive.…”

Section: Discussionmentioning

confidence: 99%

Clusterin enhances AKT2‐mediated motility of normal and cancer prostate cells through a PTEN and PHLPP1 circuit

Bertacchini

Mediani

Beretti

et al. 2018

Journal Cellular Physiology

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Clusterin (CLU) is a chaperone‐like protein with multiple functions. sCLU is frequently upregulated in prostate tumor cells after chemo‐ or radiotherapy and after surgical or pharmacological castration. Moreover, CLU has been documented to modulate the cellular homolog of murine thymoma virus akt8 oncogene (AKT) activity. Here, we investigated how CLU overexpression influences phosphatidylinositol 3′‐kinase (PI3K)/AKT signaling in human normal and cancer epithelial prostate cells. Human prostate cells stably transfected with CLU were broadly profiled by reverse phase protein array (RPPA), with particular emphasis on the PI3K/AKT pathway. The effect of CLU overexpression on normal and cancer cell motility was also tested. Our results clearly indicate that CLU overexpression enhances phosphorylation of AKT restricted to isoform 2. Mechanistically, this can be explained by the finding that the phosphatase PH domain leucine‐rich repeat‐containing protein phosphatase 1 (PHLPP1), known to dephosphorylate AKT2 at S474, is markedly downregulated by CLU, whereas miR‐190, a negative regulator of PHLPP1, is upregulated. Moreover, we found that phosphatase and tensin homolog (PTEN) was heavily phosphorylated at the inhibitory site S380, contributing to the hyperactivation of AKT signaling. By keeping AKT2 phosphorylation high, CLU dramatically enhances the migratory behavior of prostate epithelial cell lines with different migratory and invasive phenotypes, namely prostate normal epithelial 1A (PNT1A) and prostatic carcinoma 3 (PC3) cells. Altogether, our results unravel for the first time a circuit by which CLU can switch a low migration phenotype toward a high migration phenotype, through miR‐190‐dependent downmodulation of PHLPP1 expression and, in turn, stabilization of AKT2 phosphorylation.

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“…sCLU increase the resistance of HCC cells to chemotherapy by interacting with AKT and Bcl-2 / Bax pathway 25 . In pancreatic cancer, prostate cancer and other tumors, also observed increased sCLU expression, and increased resistance of tumor cells to chemotherapeutic drugs, while blocking the expression of sCLU protein increased the sensitivity of chemotherapy 26 , 27 . To analyze the relationship between GP73 and sCLU, we detected the expression of sCLU in OXA resistant HCC cell lines with different GP73 expression levels.…”

Section: Discussionmentioning

confidence: 97%

GP73 level determines chemotherapeutic resistance in human hepatocellular carcinoma cells

Ye¹,

Yan²,

Yuan³

et al. 2018

J. Cancer

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Objective GP73 is a new hepatocellular carcinoma (HCC) marker, which is highly expressed in hepatocellular carcinoma and closely relates to prognosis. This study was to investigate the effects of GP73 on cellular proliferation, apoptosis, oxaliplatin (OXA) resistance and secretory clusterin (sCLU) of HCC cells.Materials and Methods Western blot and immunofluorescence was used to detect the expression of GP73 in 8 types of commonly used HCC cell lines. Drug resistance was induced by increasing concentration gradient method. The drug-resistant human HCC cell lines underwent GP73 overexpression or inhibition. Flow cytometry were used to detect the proliferation and apoptosis of HCC cell lines. The changes of sCLU were detected by enzyme-linked immunosorbent assay (ELISA).Results The expression of GP73 in MHC-97H cells was the highest and in Hep3B cells the lowest. The expression of GP73 was found further elevated in OXA-resistant MHC-97H cells. After the knockdown of GP73 in OXA-resistant 97H cells, the IC50 of OXA decreased and the ability of cell proliferation decreased significantly. After over-expression of GP73 in OXA-resistant Hep3B cells, the IC50 of OXA increased and the cell proliferation ability increased, showing that GP73 is critical for OXA resistant in HCC cell lines; No significant change of sCLU level in GP73 overexpressed Hep3B and GP73 blocked MHCC-97H were identified.Conclusion The expression level of GP73 is critical for the resistance of OXA in HCC cell lines.

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Clinical significance of clusterin expression in pancreatic adenocarcinoma

Cited by 9 publications

References 30 publications

Apolipoproteins and cancer

Apolipoproteins and cancer

Clusterin enhances AKT2‐mediated motility of normal and cancer prostate cells through a PTEN and PHLPP1 circuit

GP73 level determines chemotherapeutic resistance in human hepatocellular carcinoma cells

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