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CD133 initiates tumors, induces epithelial-mesenchymal transition and increases metastasis in pancreatic cancer.

Nomura A, Banerjee S, Chugh R, Dudeja V, Yamamoto M, Vickers SM, Saluja AK - Oncotarget (2015)

Bottom Line: Additionally, CD133 expression induced epithelial-mesenchymal transition (EMT) and increased in vitro invasion.EMT induction and increased invasiveness were mediated by NF-κB activation, as inhibition of NF-κB mitigated these effects.This study showed that CD133 expression contributes to pancreatic cancer "stemness," tumorigenicity, EMT induction, invasion, and metastasis.

View Article: PubMed Central - PubMed

Affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.

ABSTRACT
CD133 has been implicated as a cancer stem cell (CSC) surface marker in several malignancies including pancreatic cancer. However, the functional role of this surface glycoprotein in the cancer stem cell remains elusive. In this study, we determined that CD133 overexpression induced "stemness" properties in MIA-PaCa2 cells along with increased tumorigenicity, tumor progression, and metastasis in vivo. Additionally, CD133 expression induced epithelial-mesenchymal transition (EMT) and increased in vitro invasion. EMT induction and increased invasiveness were mediated by NF-κB activation, as inhibition of NF-κB mitigated these effects. This study showed that CD133 expression contributes to pancreatic cancer "stemness," tumorigenicity, EMT induction, invasion, and metastasis.

No MeSH data available.


Related in: MedlinePlus

CD133 induced NF-κB activation promotes epithelial-mesenchymal transition and increases invasiveness(A) NF-κB activity correlated with CD133 expression and (B)In vitro invasion was decreased by NF-κB inhibition through IKK repression and pharmacological BAY 11–7085 treatment. (C) Decreased EMT genes upon IKBα repression in CD133hi-MIA cells and (D) induction of NF-κB activity through IKK enhancer plasmid in EV-MIA control increased EMT related genes and conversely.
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Figure 5: CD133 induced NF-κB activation promotes epithelial-mesenchymal transition and increases invasiveness(A) NF-κB activity correlated with CD133 expression and (B)In vitro invasion was decreased by NF-κB inhibition through IKK repression and pharmacological BAY 11–7085 treatment. (C) Decreased EMT genes upon IKBα repression in CD133hi-MIA cells and (D) induction of NF-κB activity through IKK enhancer plasmid in EV-MIA control increased EMT related genes and conversely.

Mentions: NF-κB has been reported to regulate EMT and invasion [15, 16, 18]. We and others have demonstrated that CD133+ cells have increased activity of the NF-κB pathway as compared with CD133− cells [7, 19, 20]. To determine if CD133 mediated the increased invasiveness and if EMT induction was regulated by NF-κB, we studied its activity in CD133hi-MIA cells using a dual luciferase assay. NF-κB activity was significantly increased in CD133hi-MIA cells (2.9 fold) (Figure 5A) compared with MIA PaCa-2. This increased activity further correlated with in vitro invasion, as determined by Boyden chamber invasion assay (Figure 5B).


CD133 initiates tumors, induces epithelial-mesenchymal transition and increases metastasis in pancreatic cancer.

Nomura A, Banerjee S, Chugh R, Dudeja V, Yamamoto M, Vickers SM, Saluja AK - Oncotarget (2015)

CD133 induced NF-κB activation promotes epithelial-mesenchymal transition and increases invasiveness(A) NF-κB activity correlated with CD133 expression and (B)In vitro invasion was decreased by NF-κB inhibition through IKK repression and pharmacological BAY 11–7085 treatment. (C) Decreased EMT genes upon IKBα repression in CD133hi-MIA cells and (D) induction of NF-κB activity through IKK enhancer plasmid in EV-MIA control increased EMT related genes and conversely.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480754&req=5

Figure 5: CD133 induced NF-κB activation promotes epithelial-mesenchymal transition and increases invasiveness(A) NF-κB activity correlated with CD133 expression and (B)In vitro invasion was decreased by NF-κB inhibition through IKK repression and pharmacological BAY 11–7085 treatment. (C) Decreased EMT genes upon IKBα repression in CD133hi-MIA cells and (D) induction of NF-κB activity through IKK enhancer plasmid in EV-MIA control increased EMT related genes and conversely.
Mentions: NF-κB has been reported to regulate EMT and invasion [15, 16, 18]. We and others have demonstrated that CD133+ cells have increased activity of the NF-κB pathway as compared with CD133− cells [7, 19, 20]. To determine if CD133 mediated the increased invasiveness and if EMT induction was regulated by NF-κB, we studied its activity in CD133hi-MIA cells using a dual luciferase assay. NF-κB activity was significantly increased in CD133hi-MIA cells (2.9 fold) (Figure 5A) compared with MIA PaCa-2. This increased activity further correlated with in vitro invasion, as determined by Boyden chamber invasion assay (Figure 5B).

Bottom Line: Additionally, CD133 expression induced epithelial-mesenchymal transition (EMT) and increased in vitro invasion.EMT induction and increased invasiveness were mediated by NF-κB activation, as inhibition of NF-κB mitigated these effects.This study showed that CD133 expression contributes to pancreatic cancer "stemness," tumorigenicity, EMT induction, invasion, and metastasis.

View Article: PubMed Central - PubMed

Affiliation: Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.

ABSTRACT
CD133 has been implicated as a cancer stem cell (CSC) surface marker in several malignancies including pancreatic cancer. However, the functional role of this surface glycoprotein in the cancer stem cell remains elusive. In this study, we determined that CD133 overexpression induced "stemness" properties in MIA-PaCa2 cells along with increased tumorigenicity, tumor progression, and metastasis in vivo. Additionally, CD133 expression induced epithelial-mesenchymal transition (EMT) and increased in vitro invasion. EMT induction and increased invasiveness were mediated by NF-κB activation, as inhibition of NF-κB mitigated these effects. This study showed that CD133 expression contributes to pancreatic cancer "stemness," tumorigenicity, EMT induction, invasion, and metastasis.

No MeSH data available.


Related in: MedlinePlus