Up-regulation of 14-3-3ζ expression in intrahepatic cholangiocarcinoma and its clinical implications

Zhang, Chi; Liu, Lixin; Dong, Zhao‐Ru; Shi, Guohai; Cai, Jia‐Bin; Zhang, Peng-Fei; Ke, Ai–Wu; Yu, Jingxian; Zhou, Jian; Fan, Jia

doi:10.1007/s13277-014-2780-5

Cited by 28 publications

(32 citation statements)

References 31 publications

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“…Neal et al also reported that an elevated level of 14-3-3ζ was associated with reduced survival and increased recurrence in breast cancer [14]. Moreover, Zhang et al reported that 14-3-3ζ overexpression indicated poor prognosis of intrahepatic cholangiocarcinoma in terms of a shorter patient survival and a higher recurrence [19]. In our previous study, we reported that 14-3-3ζ overexpression was significantly correlated with a shorter survival time and a higher recurrence rate in HCC [20].…”

Section: Discussionmentioning

confidence: 97%

“…Of types of the 14-3-3 proteins, 14-3-3ζ has been found to promote anchorage-independent growth and proliferation, inhibit apoptosis, and enhance chemo-resistance and metastasis of cancer cells [11,12]. In addition, a high level of 14-3-3ζ is correlated with poor prognosis of multiple cancers, including breast cancer [13,14], non-small cell lung cancer [15][16][17], gastric carcinoma [18], intrahepatic cholangiocarcinoma [19], and HCC [20]. A previous study showed that overexpression of 14-3-3ζ could lead to the activation of Akt in human mammary epithelial cells [21].…”

Section: Introductionmentioning

confidence: 99%

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Co-Upregulation of 14-3-3ζ and P-Akt is Associated with Oncogenesis and Recurrence of Hepatocellular Carcinoma

Tang

Wang

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: 14-3-3ζ is involved in the regulation of PI3K/Akt pathway which is closely associated with carcinogenesis. However, the clinical significance of combined detection of 14-3-3ζ and p-Akt in hepatocellular carcinoma (HCC) remains unclear. Methods: Two-hundred pairs of HCC and adjacent liver specimens were subjected to tissue microarray. The association of 14-3-3ζ and p-Akt levels with the postoperative survival and recurrence in HCC patients was analyzed with univariate and multivariate methods. Moreover, the effects of 14-3-3ζ overexpression on the growth of HCC and the expressions of p-Akt and HIF-1α were assessed in a xenograft mouse model. Results: Elevated levels of 14-3-3ζ and p-Akt were detected in HCC and a positive correlation between the levels of 14-3-3ζ and p-Akt was verified. HCC patients with satellite nodules, microvascular invasion, portal vein tumor thrombosis, poor tumor differentiation and an advanced tumor stage tended to have higher levels of 14-3-3ζ and p-Akt. In addition, the postoperative 3-, 5-, and 7-year overall survival rates in HCC patients with 14-3-3ζhigh and p-Akthigh were significantly lower compared with those with 14-3-3ζlow and p-Aktlow, and the cumulative recurrence rate in HCC patients with 14-3-3ζhigh and p-Akthigh was significantly higher than that in those with 14-3-3ζlow and p-Aktlow. The multivariate Cox proportional hazard analysis indicated that concomitant upregulation of 14-3-3ζ and p-Akt was an independent factor that predicted poor survival and high recurrence in HCC patients. Furthermore, animal experiment showed that overexpression of 14-3-3ζ accelerated the growth of HCC xenograft tumors and induced the expressions of p-Akt and HIF-1α in vivo. Conclusion: Co-upregulation of 14-3-3ζ and p-Akt predicts poor prognosis in patients with HCC, and 14-3-3ζ-induced activation of the Akt signaling pathway contributes to HCC progression.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Co-Upregulation of 14-3-3ζ and P-Akt is Associated with Oncogenesis and Recurrence of Hepatocellular Carcinoma

Tang

Wang

Zhang

et al. 2018

Cell Physiol Biochem

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“…Inclusion criteria were described in our previous study 16. Ethical approval was obtained from Zhongshan Hospital Research Ethics Committee, and all patients signed an informed consent form.…”

Section: Methodsmentioning

confidence: 99%

“…Tissue microarray (TMA) was constructed and immunohistochemistry (IHC) was performed as described in our previous study 16. The antibodies used for IHC are listed in online supplementary table S1.…”

Section: Methodsmentioning

confidence: 99%

Mortalin promotes cell proliferation and epithelial mesenchymal transition of intrahepatic cholangiocarcinoma cells in vitro

et al. 2017

Self Cite

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“…In addition, 14-3-3zeta and aPKC-ι [121,122], adrenomedullin [123], Forkhead box protein C2 [124], WAVE3 [125] and Fibroblast growth factor (FGF)19/FGFR4 axis [126] promote EMT in CCA. Conversely, FBXW7 [127,128], thymosin β10 [129] and MAP3K4 [130] act as negative regulators of EMT through inhibition of mTOR, ERK1/2 and NFκB pathways, respectively.…”

Section: Additional Regulatory Factorsmentioning

confidence: 99%

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

Vaquero

Guedj

Clapéron

et al. 2017

Journal of Hepatology

125

122

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Cholangiocarcinoma (CCA) is an aggressive tumor with a poor prognosis due to its late clinical presentation and the lack of effective non-surgical therapies. Unfortunately, most of the patients are not eligible for curative surgery owing to the presence of metastases at the time of diagnosis. Therefore, it is important to understand the steps leading to cell dissemination in patients with CCA. To metastasize from the primary site, cancer cells must acquire migratory and invasive properties by a cell plasticity-promoting phenomenon known as epithelial-mesenchymal transition (EMT). EMT is a reversible dynamic process by which epithelial cells gradually adopt structural and functional characteristics of mesenchymal cells, and has lately become a center of attention in the field of metastatic dissemination. In the present review, we aim to provide an extensive overview of the current clinical data and the prognostic value of different EMT markers that have been analyzed in CCA. We summarize all the regulatory networks implicated in EMT from the membrane receptors to the main EMT-inducing transcription factors (SNAIL, TWIST and ZEB). Furthermore, since a tumor is a complex structure not exclusively formed by tumor cells, we also address the prominent role of the main cell types of the desmoplastic stroma that characterizes CCA in the regulation of EMT. Finally, we discuss the therapeutic considerations and difficulties faced to develop an effective anti-EMT treatment due to the redundancies and bypasses among the pathways regulating EMT. 4Key Point Box -EMT is an early event of metastasis that endows tumor cells with invasive properties enabling them to spread toward other territories.-EMT contributes to CCA progression and chemoresistance.-The three families of transcription factors that regulate epithelial and mesenchymal marker expression during EMT (SNAIL, TWIST and ZEB) contribute to CCA progression.-Cells of CCA microenvironment, and not only cancer cells, lead to the activation of EMT.

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Up-regulation of 14-3-3ζ expression in intrahepatic cholangiocarcinoma and its clinical implications

Cited by 28 publications

References 31 publications

Co-Upregulation of 14-3-3ζ and P-Akt is Associated with Oncogenesis and Recurrence of Hepatocellular Carcinoma

Co-Upregulation of 14-3-3ζ and P-Akt is Associated with Oncogenesis and Recurrence of Hepatocellular Carcinoma

Mortalin promotes cell proliferation and epithelial mesenchymal transition of intrahepatic cholangiocarcinoma cells in vitro

Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks

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