<i>Gli1</i>contributes to the invasiveness of pancreatic cancer through matrix metalloproteinase‐9 activation

Nagai, Sonoko; Nakamura, Masafumi; Yanai, Kosuke; Wada, Junji; Akiyoshi, Takashi; Nakashima, Hiroshi; Ohuchida, Kenoki; Sato, Norihiro; Tanaka, Masao; Katano, Mitsuo

doi:10.1111/j.1349-7006.2008.00822.x

Cited by 66 publications

(63 citation statements)

References 27 publications

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“…Furthermore, it was identified that the mRNA and protein levels of Gli1, TGF-β1 and CXCR4 were coordinately downregulated in the cyclopamine-treated AGS cells, and that the quantity of TGF-β1 secreted into the culture supernatant was significantly reduced following a 24-h treatment with 5 and 10 µM cyclopamine. These findings are in agreement with a number of previously conducted studies (25,36,37). To further elucidate the role of Hh as an important regulator in AGS cells, the present study demonstrated that the Hh signaling pathway appears to regulate tumor invasion and metastasis via TGF-β1 and CXCR4.…”

Section: Discussionsupporting

confidence: 82%

“…The Hh signaling pathway was initially recognized for its role in modulating embryonic cell proliferation and differentiation (1-4); however, more recently, it has been demonstrated that Hh is important in the proliferation of various types of cancer cells, including lung, pancreatic and gastric cancer cells (12,14,16,(24)(25)(26). While the mechanisms of the Hh signaling pathway in promoting gastric tumorigenesis and regulating downstream target genes are largely unknown, various lines of evidence indicate that a number of key factors, such as TGF-β1 and CXCR4, are actively involved.…”

Section: Discussionmentioning

confidence: 99%

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Effects and mechanisms of blocking the hedgehog signaling pathway in human gastric cancer cells

Cong-zhi

et al. 2015

Oncology Letters

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Abstract. Excessive activation of the hedgehog (Hh) signaling pathway is important in a variety of human cancer cell types, including gastric cancer. However, the underlying mechanisms of the Hh signaling pathway in inducing gastric tumorigenesis and its downstream target genes are largely unknown. In the present study, the inhibitory effect of cyclopamine on the Hh signaling pathway was investigated in the human gastric cancer AGS cell line. It was identified that cyclopamine treatment inhibited the proliferation, migration and invasion of the AGS cells in a dose-and time-dependent manner, and resulted in the downregulation of a number of key Hh signaling pathway-associated factors [glioma-associated oncogene homolog 1, C-X-C chemokine receptor type 4 and transforming growth factor (TGF)-β1] at the RNA and protein levels. Furthermore, the secretion of TGF-β1 was significantly reduced following the administration of cyclopamine to the AGS cells. The results of the present study provided insight into the mechanisms by which the Hh signaling pathway regulates gastric cancer formation and identified the Hh signaling pathway as a potential novel therapeutic target in human gastric cancer.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Effects and mechanisms of blocking the hedgehog signaling pathway in human gastric cancer cells

Cong-zhi

et al. 2015

Oncology Letters

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“…Although it has been confirmed that the Hh pathway participates in cell migration and angiogenesis processes and is correlated with the severity of the associated tumor (27)(28)(29), additionally, disruption of Hh pathway has been shown to inhibit metastasis in pancreatic cancer and gastric cancer (29)(30)(31), the relationship between the Hh signaling pathway and aggressiveness of HCC cells remains unclear. It is necessary to investigate whether the signaling influences proliferative and invasive potential of HCC cells.…”

Section: Discussionmentioning

confidence: 99%

Role of Hedgehog signaling pathway in proliferation and invasiveness of hepatocellular carcinoma cells

Cheng

Xu²,

Tian³

et al. 2009

Int J Oncol

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Abstract. The Hedgehog (Hh) pathway has been confirmed a contributor to the carcinogenesis and progression of various tumor types. To investigate the Hh signaling activity in human hepatocellular carcinoma (HCC), we detected the expression levels of Hh pathway components (Shh, Ptch1 and Gli2) in 57 samples of HCC and corresponding adjacent-tumor liver tissues. The Hh pathway was overexpressed in cancer tissues compared with non-cancer tissues and correlated closely with histologic differentiation and portal venous invasion of HCC. To elucidate the relationship between Hh signaling and HCC progression, we performed a further study in vitro. First, the expression levels of the signaling were detected in a subset of hepatoma cell lines and SMMC-7721 cells selected with high level of Hh signaling expression. Next, we employed KAAD-cyclopamine (a specific inhibitor of Hedgehog pathway) to block the Hh pathway in SMMC-7721 cells and assessed the changes of their biological behaviors. The results showed that the blockade of Hh signaling pathway by KAAD-cyclopamine induced reduction of DNA synthesis leading to marked cell growth inhibition and also caused significant attenuation in invasiveness and motility of HCC cells. Collectively, our data demonstrated that the Hh pathway plays an important role in HCC development and invasion. Blockade of the Hh signaling pathway may be a potential target of new therapeutic strategy for HCC.

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“…Recently, matrix metalloproteinase-9 (MMP-9) and ER were shown to increase invasiveness through activation of the Hh pathway. (50,52) Nagai et al (52) showed that Gli1 contributes to the invasiveness of pancreatic cancer. Moreover, we reported that Hh signaling contributes to invasiveness under hypoxic conditions, which is observed in regions that are distant from the supporting tumor vasculature and is characteristic of pancreatic cancer.…”

Section: Contribution Of the Hh Signaling Pathway To Cancer Progressimentioning

confidence: 99%

Hedgehog signaling pathway as a therapeutic target in various types of cancer

Onishi¹,

Katano

2011

Cancer Science

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Hedgehog (Hh) signaling is an important factor in growth and patterning during embryonic development. A mutation in Patched, Smoothened or Gli1, which regulate the Hh signaling pathway, might lead to the onset of glioblastoma, basal cell carcinoma, medulloblastoma and rhabdomyosarcoma. Recently, Hh signaling has been reported to be activated in a ligand‐dependent manner, contributing to carcinogenesis and cancer progression. Hedgehog signaling is reactivated in various types of cancer, and this contributes to cancer progression by facilitating proliferation, invasion and cell survival. Moreover, Hh signaling is associated with several other signaling pathways that contribute to cancer progression. These observations indicate that controlling Hh signaling might become a target for novel molecular targeting therapy. (Cancer Sci 2011; 102: 1756–1760)

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Gli1contributes to the invasiveness of pancreatic cancer through matrix metalloproteinase‐9 activation

Cited by 66 publications

References 27 publications

Effects and mechanisms of blocking the hedgehog signaling pathway in human gastric cancer cells

Effects and mechanisms of blocking the hedgehog signaling pathway in human gastric cancer cells

Role of Hedgehog signaling pathway in proliferation and invasiveness of hepatocellular carcinoma cells

Hedgehog signaling pathway as a therapeutic target in various types of cancer

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