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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

Immunohistochemistry analysis of YAP and TAZ/WWTR1 in normal human pancreas.(A,B) Immunohistochemistry analysis of normal human pancreatic tissue using anti-YAP antibody (H125); Two representative fields of the same sample are shown. Specimens obtained from an additional three individuals were also analyzed and shown in Supplemental Figure S2. The islet of Langerhans is indicated. Magnification: 20 x, error bar: 100 μm. (C,D) Immunohistochemistry analysis of normal human pancreatic tissue using anti-TAZ/WWTR1 antibody. Two representative fields of the same sample are shown. The islet of Langerhans is indicated. Magnification: 20 x, error bar: 100 μm.
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f1: Immunohistochemistry analysis of YAP and TAZ/WWTR1 in normal human pancreas.(A,B) Immunohistochemistry analysis of normal human pancreatic tissue using anti-YAP antibody (H125); Two representative fields of the same sample are shown. Specimens obtained from an additional three individuals were also analyzed and shown in Supplemental Figure S2. The islet of Langerhans is indicated. Magnification: 20 x, error bar: 100 μm. (C,D) Immunohistochemistry analysis of normal human pancreatic tissue using anti-TAZ/WWTR1 antibody. Two representative fields of the same sample are shown. The islet of Langerhans is indicated. Magnification: 20 x, error bar: 100 μm.

Mentions: We performed immunohistochemistry to examine the expression patterns of YAP and TAZ/WWTR1 in normal human pancreatic tissues obtained from four individuals. The YAP expression patterns resemble those of the centroacinar cells and ductal cells (Fig. 1), the subpopulations of the exocrine compartments that are implicated in having certain stem cell properties during tissue regeneration following injury272829303132. In these cells, YAP and TAZ show diffused localization and the proteins can be found in both nuclei and cytoplasm (Fig. 1). In contrast, YAP is not expressed in acinar cells, or in islets of Langerhans (Fig. 1). These expression patterns of YAP were confirmed using three additional anti-YAP antibodies, including antibodies specific for the S127 phosphorylated form of YAP (Supplemental Figure S1). Furthermore, we observed similar centroacinar/ductal localization patterns for TAZ (Fig. 1).


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)

Immunohistochemistry analysis of YAP and TAZ/WWTR1 in normal human pancreas.(A,B) Immunohistochemistry analysis of normal human pancreatic tissue using anti-YAP antibody (H125); Two representative fields of the same sample are shown. Specimens obtained from an additional three individuals were also analyzed and shown in Supplemental Figure S2. The islet of Langerhans is indicated. Magnification: 20 x, error bar: 100 μm. (C,D) Immunohistochemistry analysis of normal human pancreatic tissue using anti-TAZ/WWTR1 antibody. Two representative fields of the same sample are shown. The islet of Langerhans is indicated. 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

f1: Immunohistochemistry analysis of YAP and TAZ/WWTR1 in normal human pancreas.(A,B) Immunohistochemistry analysis of normal human pancreatic tissue using anti-YAP antibody (H125); Two representative fields of the same sample are shown. Specimens obtained from an additional three individuals were also analyzed and shown in Supplemental Figure S2. The islet of Langerhans is indicated. Magnification: 20 x, error bar: 100 μm. (C,D) Immunohistochemistry analysis of normal human pancreatic tissue using anti-TAZ/WWTR1 antibody. Two representative fields of the same sample are shown. The islet of Langerhans is indicated. Magnification: 20 x, error bar: 100 μm.
Mentions: We performed immunohistochemistry to examine the expression patterns of YAP and TAZ/WWTR1 in normal human pancreatic tissues obtained from four individuals. The YAP expression patterns resemble those of the centroacinar cells and ductal cells (Fig. 1), the subpopulations of the exocrine compartments that are implicated in having certain stem cell properties during tissue regeneration following injury272829303132. In these cells, YAP and TAZ show diffused localization and the proteins can be found in both nuclei and cytoplasm (Fig. 1). In contrast, YAP is not expressed in acinar cells, or in islets of Langerhans (Fig. 1). These expression patterns of YAP were confirmed using three additional anti-YAP antibodies, including antibodies specific for the S127 phosphorylated form of YAP (Supplemental Figure S1). Furthermore, we observed similar centroacinar/ductal localization patterns for TAZ (Fig. 1).

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