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Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis.

Morvaridi S, Dhall D, Greene MI, Pandol SJ, Wang Q - Sci Rep (2015)

Bottom Line: Using human tissues we show that YAP and TAZ expression is restricted to the centroacinar and ductal cells of normal pancreas, but is elevated in cancer cells.In particular, YAP and TAZ are expressed at high levels in the activated stellate cells of both chronic pancreatitis and PDAC patients as well as in the islets of Langerhans in chronic pancreatitis tissues.Of note, YAP is up regulated in both acinar and ductal cells following induction of acute and chronic pancreatitis in mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine; Cedars-Sinai Medical Center, Los Angeles, CA 90048.

ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic and inflammatory microenvironment that is formed primarily by activated, myofibroblast-like, stellate cells. Although the stellate cells are thought to contribute to tumorigenesis, metastasis and drug resistance of PDAC, the signaling events involved in activation of the stellate cells are not well defined. Functioning as transcription co-factors, Yes-associated protein (YAP) and its homolog transcriptional co-activator with PDZ-binding motif (TAZ) modulate the expression of genes involved in various aspects of cellular functions, such as proliferation and mobility. Using human tissues we show that YAP and TAZ expression is restricted to the centroacinar and ductal cells of normal pancreas, but is elevated in cancer cells. In particular, YAP and TAZ are expressed at high levels in the activated stellate cells of both chronic pancreatitis and PDAC patients as well as in the islets of Langerhans in chronic pancreatitis tissues. Of note, YAP is up regulated in both acinar and ductal cells following induction of acute and chronic pancreatitis in mice. These findings indicate that YAP and TAZ may play a critical role in modulating pancreatic tissue regeneration, neoplastic transformation, and stellate cell functions in both PDAC and pancreatitis.

No MeSH data available.


Related in: MedlinePlus

YAP and TAZ/WWTR1 expression in human chronic pancreatitis (CP) tissues.(A) Chronic pancreatitis tissue isolated from CP patient #1, stained using anti-YAP antibody (H125). Specimens obtained from an additional three individuals were also analyzed and shown in Supplemental Figure S3. Representative images are shown. (B) Chronic pancreatitis tissue (CP#1) stained using anti-WWTR1/TAZ antibody. The arrowheads indicate expression of YAP or TAZ in stellate cells. Magnification: 20 x, error bar: 100 μm.
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f5: YAP and TAZ/WWTR1 expression in human chronic pancreatitis (CP) tissues.(A) Chronic pancreatitis tissue isolated from CP patient #1, stained using anti-YAP antibody (H125). Specimens obtained from an additional three individuals were also analyzed and shown in Supplemental Figure S3. Representative images are shown. (B) Chronic pancreatitis tissue (CP#1) stained using anti-WWTR1/TAZ antibody. The arrowheads indicate expression of YAP or TAZ in stellate cells. Magnification: 20 x, error bar: 100 μm.

Mentions: Notably, in tissues of chronic pancreatitis, YAP and TAZ levels are expressed in a sub-population of stromal cells (Fig. 5 and Supplemental Figure S3). YAP and TAZ levels also appear to be elevated in the islets of Langerhans in the chronic pancreatitis tissue in contrast to normal pancreas. The localization is predominantly nuclear in the islet cells (Fig. 5 and Supplemental Figure S3).


Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis.

Morvaridi S, Dhall D, Greene MI, Pandol SJ, Wang Q - Sci Rep (2015)

YAP and TAZ/WWTR1 expression in human chronic pancreatitis (CP) tissues.(A) Chronic pancreatitis tissue isolated from CP patient #1, stained using anti-YAP antibody (H125). Specimens obtained from an additional three individuals were also analyzed and shown in Supplemental Figure S3. Representative images are shown. (B) Chronic pancreatitis tissue (CP#1) stained using anti-WWTR1/TAZ antibody. The arrowheads indicate expression of YAP or TAZ in stellate cells. Magnification: 20 x, error bar: 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4645184&req=5

f5: YAP and TAZ/WWTR1 expression in human chronic pancreatitis (CP) tissues.(A) Chronic pancreatitis tissue isolated from CP patient #1, stained using anti-YAP antibody (H125). Specimens obtained from an additional three individuals were also analyzed and shown in Supplemental Figure S3. Representative images are shown. (B) Chronic pancreatitis tissue (CP#1) stained using anti-WWTR1/TAZ antibody. The arrowheads indicate expression of YAP or TAZ in stellate cells. Magnification: 20 x, error bar: 100 μm.
Mentions: Notably, in tissues of chronic pancreatitis, YAP and TAZ levels are expressed in a sub-population of stromal cells (Fig. 5 and Supplemental Figure S3). YAP and TAZ levels also appear to be elevated in the islets of Langerhans in the chronic pancreatitis tissue in contrast to normal pancreas. The localization is predominantly nuclear in the islet cells (Fig. 5 and Supplemental Figure S3).

Bottom Line: Using human tissues we show that YAP and TAZ expression is restricted to the centroacinar and ductal cells of normal pancreas, but is elevated in cancer cells.In particular, YAP and TAZ are expressed at high levels in the activated stellate cells of both chronic pancreatitis and PDAC patients as well as in the islets of Langerhans in chronic pancreatitis tissues.Of note, YAP is up regulated in both acinar and ductal cells following induction of acute and chronic pancreatitis in mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine; Cedars-Sinai Medical Center, Los Angeles, CA 90048.

ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic and inflammatory microenvironment that is formed primarily by activated, myofibroblast-like, stellate cells. Although the stellate cells are thought to contribute to tumorigenesis, metastasis and drug resistance of PDAC, the signaling events involved in activation of the stellate cells are not well defined. Functioning as transcription co-factors, Yes-associated protein (YAP) and its homolog transcriptional co-activator with PDZ-binding motif (TAZ) modulate the expression of genes involved in various aspects of cellular functions, such as proliferation and mobility. Using human tissues we show that YAP and TAZ expression is restricted to the centroacinar and ductal cells of normal pancreas, but is elevated in cancer cells. In particular, YAP and TAZ are expressed at high levels in the activated stellate cells of both chronic pancreatitis and PDAC patients as well as in the islets of Langerhans in chronic pancreatitis tissues. Of note, YAP is up regulated in both acinar and ductal cells following induction of acute and chronic pancreatitis in mice. These findings indicate that YAP and TAZ may play a critical role in modulating pancreatic tissue regeneration, neoplastic transformation, and stellate cell functions in both PDAC and pancreatitis.

No MeSH data available.


Related in: MedlinePlus