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Zipper-interacting protein kinase promotes epithelial-mesenchymal transition, invasion and metastasis through AKT and NF-kB signaling and is associated with metastasis and poor prognosis in gastric cancer patients.

Li J, Deng Z, Wang Z, Wang D, Zhang L, Su Q, Lai Y, Li B, Luo Z, Chen X, Chen Y, Huang X, Ma J, Wang W, Bi J, Guan X - Oncotarget (2015)

Bottom Line: Zipper-interacting Protein Kinase (ZIPK) belongs to the death-associated protein kinase family.Increased expression of ZIPK in lymph node metastases was significantly associated with stage VI and abdominal organ invasion.Survival analysis revealed that patients with increased ZIPK expression in metastatic lymph nodes had poor disease-specific survival.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.

ABSTRACT
Zipper-interacting Protein Kinase (ZIPK) belongs to the death-associated protein kinase family. ZIPK has been characterized as a tumor suppressor in various tumors, including gastric cancer. On the other hand, ZIPK also promotes cell survival. In this study, both in vitro and in vivo assays indicated that ZIPK promoted cell growth, proliferation, migration, invasion, tumor formation and metastasis in nude mice. ZIPK induced epithelial-mesenchymal transition (EMT) with increasing expression of β-catenin, mesenchymal markers, Snail and Slug, and with decreasing expression of E-cadherin. Furthermore, ZIPK activated the AKT/IκB/NF-κB pathway, which can promote EMT and metastasis. Additionally, ZIPK expression was detected in human primary gastric cancer and their matched metastatic lymph node samples by immunohistochemistry. Increased expression of ZIPK in lymph node metastases was significantly associated with stage VI and abdominal organ invasion. Survival analysis revealed that patients with increased ZIPK expression in metastatic lymph nodes had poor disease-specific survival. Taken together, our study reveals that ZIPK is a pro-oncogenic factor, which promotes cancer metastasis.

No MeSH data available.


Related in: MedlinePlus

ZIPK enhances stemness of gastric cancer cells(A) Quantitative real-time PCR analysis showed the elevated expression of Oct-4, Nanog, ABCG2, CD44, CD24 and CD133 in ZIPK-transfected cells compared with control cells (**indicates P < 0.01; ***indicates P < 0.001, independent Student's t-test). (B) Flow cytometry analysis showed the higher mean flourscence indensity of FITC-CD44, PE-CD24, and PE-CD133 in ZIPK-transfected cells (**indicates P < 0.01, independent Student's t-test).
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Figure 6: ZIPK enhances stemness of gastric cancer cells(A) Quantitative real-time PCR analysis showed the elevated expression of Oct-4, Nanog, ABCG2, CD44, CD24 and CD133 in ZIPK-transfected cells compared with control cells (**indicates P < 0.01; ***indicates P < 0.001, independent Student's t-test). (B) Flow cytometry analysis showed the higher mean flourscence indensity of FITC-CD44, PE-CD24, and PE-CD133 in ZIPK-transfected cells (**indicates P < 0.01, independent Student's t-test).

Mentions: There is emerging evidence that the EMT process may give rise to cancer stem cells (CSCs) or cells with stem cell-like properties. We further examined if ZIPK could increase stemness of gastric cancer cells by determining expression levels of stemness-associated genes through qRT-PCR. The results showed that stemness genes (Nanog and Oct-4), multiple drug-resistant transporter gene (ABCG2) and surface antigens associated with cancer stem cells (CD24, CD44 and CD133) were upregulated in ZIPK-transfected cells compared with control cells (Figure 6A). Flow cytometry assay showed that the expression level of CD44, CD24 and CD133 was high in ZIPK-transfected cells (Figure 6B).


Zipper-interacting protein kinase promotes epithelial-mesenchymal transition, invasion and metastasis through AKT and NF-kB signaling and is associated with metastasis and poor prognosis in gastric cancer patients.

Li J, Deng Z, Wang Z, Wang D, Zhang L, Su Q, Lai Y, Li B, Luo Z, Chen X, Chen Y, Huang X, Ma J, Wang W, Bi J, Guan X - Oncotarget (2015)

ZIPK enhances stemness of gastric cancer cells(A) Quantitative real-time PCR analysis showed the elevated expression of Oct-4, Nanog, ABCG2, CD44, CD24 and CD133 in ZIPK-transfected cells compared with control cells (**indicates P < 0.01; ***indicates P < 0.001, independent Student's t-test). (B) Flow cytometry analysis showed the higher mean flourscence indensity of FITC-CD44, PE-CD24, and PE-CD133 in ZIPK-transfected cells (**indicates P < 0.01, independent Student's t-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480755&req=5

Figure 6: ZIPK enhances stemness of gastric cancer cells(A) Quantitative real-time PCR analysis showed the elevated expression of Oct-4, Nanog, ABCG2, CD44, CD24 and CD133 in ZIPK-transfected cells compared with control cells (**indicates P < 0.01; ***indicates P < 0.001, independent Student's t-test). (B) Flow cytometry analysis showed the higher mean flourscence indensity of FITC-CD44, PE-CD24, and PE-CD133 in ZIPK-transfected cells (**indicates P < 0.01, independent Student's t-test).
Mentions: There is emerging evidence that the EMT process may give rise to cancer stem cells (CSCs) or cells with stem cell-like properties. We further examined if ZIPK could increase stemness of gastric cancer cells by determining expression levels of stemness-associated genes through qRT-PCR. The results showed that stemness genes (Nanog and Oct-4), multiple drug-resistant transporter gene (ABCG2) and surface antigens associated with cancer stem cells (CD24, CD44 and CD133) were upregulated in ZIPK-transfected cells compared with control cells (Figure 6A). Flow cytometry assay showed that the expression level of CD44, CD24 and CD133 was high in ZIPK-transfected cells (Figure 6B).

Bottom Line: Zipper-interacting Protein Kinase (ZIPK) belongs to the death-associated protein kinase family.Increased expression of ZIPK in lymph node metastases was significantly associated with stage VI and abdominal organ invasion.Survival analysis revealed that patients with increased ZIPK expression in metastatic lymph nodes had poor disease-specific survival.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.

ABSTRACT
Zipper-interacting Protein Kinase (ZIPK) belongs to the death-associated protein kinase family. ZIPK has been characterized as a tumor suppressor in various tumors, including gastric cancer. On the other hand, ZIPK also promotes cell survival. In this study, both in vitro and in vivo assays indicated that ZIPK promoted cell growth, proliferation, migration, invasion, tumor formation and metastasis in nude mice. ZIPK induced epithelial-mesenchymal transition (EMT) with increasing expression of β-catenin, mesenchymal markers, Snail and Slug, and with decreasing expression of E-cadherin. Furthermore, ZIPK activated the AKT/IκB/NF-κB pathway, which can promote EMT and metastasis. Additionally, ZIPK expression was detected in human primary gastric cancer and their matched metastatic lymph node samples by immunohistochemistry. Increased expression of ZIPK in lymph node metastases was significantly associated with stage VI and abdominal organ invasion. Survival analysis revealed that patients with increased ZIPK expression in metastatic lymph nodes had poor disease-specific survival. Taken together, our study reveals that ZIPK is a pro-oncogenic factor, which promotes cancer metastasis.

No MeSH data available.


Related in: MedlinePlus