A role of activated Sonic hedgehog signaling for the cellular proliferation of oral squamous cell carcinoma cell line.
Sonic hedgehog (Shh) is a secreted morphogen crucial for appropriate cellular proliferation during mammalian development. The activated Shh signaling is known to predispose to human tumors such as medulloblastoma and basal cell carcinoma, while a role of Shh signaling in the other common tumors is still controversial. Here we showed the overexpression of Shh in five cell lines among 14 human oral squamous cell carcinoma (OSCC) cell lines. One of the Shh-expressing OSCC cell lines HSQ-89 showed the inhibition of G1/S transition and apoptotic cell death by treatment with Cyclopamine, a steroidal alkaloid that blocks the intracellular Shh signaling. Furthermore, we found that treatment with Y-27632, a specific inhibitor of Rho-associated kinase, mimicked the effect of Cyclopamine on the cell cycle progression of HSQ-89. Our study revealed the involvement of activated Shh signaling in the cellular proliferation of OSCC cells, indicating Shh signaling might be a good therapeutic target for OSCC.
Nishimaki
Haruaki
H
First Department of Pathology, Aichi Medical University School of Medicine, Nagakute, 480-1195 Aichi, Japan.
Kasai
Kenji
K
Kozaki
Ken ichi
Ki
Takeo
Tomohiro
T
Ikeda
Hiroshi
H
Saga
Shinsuke
S
Nitta
Masakazu
M
Itoh
Gen
G
D000577:Amides / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D002469:Cell Separation; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D016193:G1 Phase; D053823:Hedgehog Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009062:Mouth Neoplasms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D016196:S Phase; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014704:Veratrum Alkaloids / Q000494:pharmacology; D054460:rho-Associated Kinases
D000577:Amides; D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C509239:SHH protein, human; D015534:Trans-Activators; D014704:Veratrum Alkaloids; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C000541:cyclopamine