Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer

Shojiro Matsushita, Hideya Ohnishi, kenji nakano, Iori Nagamatsu, Akira Imaizumi, Masami Hattori, Yoshinao Oda, Masao Tanaka, Mitsuo Katano

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Gallbladder cancer (GBC) is a particularly deadly type of cancer with a 5-year survival rate of only 10%. New effective therapeutic strategies are greatly needed. Recently, we have shown that Hedgehog (Hh) signaling is reactivated in various types of cancer and is a potential therapeutic target. However, little is known about the biological significance of Hh signaling in human GBC. In this study, we determined whether Hh signaling could be a therapeutic target in GBC. The Hh transcription factor Gli1 was detected in the nucleus of GBC cells but not in the nucleus of normal gallbladder cells. The expression levels of Sonic Hh (Shh) and Smoothened (Smo) in human GBC specimens (n = 37) were higher than those in normal gallbladder tissue. The addition of exogenous Shh ligand augmented the anchor-dependent and anchor-independent proliferation and invasiveness of GBC cells in vitro. In contrast, inhibiting the effector Smo decreased the anchor-dependent and anchor-independent proliferation. Furthermore, the suppression of Smo decreased GBC cell invasiveness through the inhibition of MMP-2 and MMP-9 expression and inhibited the epithelial-mesenchymal transition. In a xenograft model, tumor volume in Smo siRNA-transfected GBC cells was significantly lower than in control tumors. These results suggest that Hh signaling is elevated in GBC and may be involved in the acquisition of malignant phenotypes, and that Hh signaling may be a potential therapeutic target for GBC.

Original languageEnglish
Pages (from-to)272-280
Number of pages9
JournalCancer Science
Volume105
Issue number3
DOIs
Publication statusPublished - Jan 1 2014

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Gallbladder Neoplasms
Therapeutics
Gallbladder
Matrix Metalloproteinases
Neoplasms
Epithelial-Mesenchymal Transition
Tumor Burden
Heterografts
Small Interfering RNA
Transcription Factors
Ligands
Phenotype

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Matsushita, S., Ohnishi, H., nakano, K., Nagamatsu, I., Imaizumi, A., Hattori, M., ... Katano, M. (2014). Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer. Cancer Science, 105(3), 272-280. https://doi.org/10.1111/cas.12354

Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer. / Matsushita, Shojiro; Ohnishi, Hideya; nakano, kenji; Nagamatsu, Iori; Imaizumi, Akira; Hattori, Masami; Oda, Yoshinao; Tanaka, Masao; Katano, Mitsuo.

In: Cancer Science, Vol. 105, No. 3, 01.01.2014, p. 272-280.

Research output: Contribution to journalArticle

Matsushita, S, Ohnishi, H, nakano, K, Nagamatsu, I, Imaizumi, A, Hattori, M, Oda, Y, Tanaka, M & Katano, M 2014, 'Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer', Cancer Science, vol. 105, no. 3, pp. 272-280. https://doi.org/10.1111/cas.12354
Matsushita S, Ohnishi H, nakano K, Nagamatsu I, Imaizumi A, Hattori M et al. Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer. Cancer Science. 2014 Jan 1;105(3):272-280. https://doi.org/10.1111/cas.12354
Matsushita, Shojiro ; Ohnishi, Hideya ; nakano, kenji ; Nagamatsu, Iori ; Imaizumi, Akira ; Hattori, Masami ; Oda, Yoshinao ; Tanaka, Masao ; Katano, Mitsuo. / Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer. In: Cancer Science. 2014 ; Vol. 105, No. 3. pp. 272-280.
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