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Updated: May 2, 2026
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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
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Suppression of Hedgehog signalling promotes pro-tumourigenic integrin expression and function
Karwan A Moutasim1, Toby Mellows, Massimiliano Mellone
1Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, SO16 6YD, UK.
The Journal of Pathology
|February 28, 2014
Summary
Hedgehog (Hh) pathway inhibition in basal cell carcinoma (BCC) unexpectedly increases αvβ6 integrin, promoting tumor cell invasion and stromal changes. This suggests a new therapeutic target for aggressive BCC and other cancers.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Aberrant Hedgehog (Hh) signaling drives malignancies like basal cell carcinoma (BCC).
- αvβ6 integrin correlates with aggressive tumors and poor prognosis.
- Previous work linked αvβ6 to invasion in morphoeic BCC variants.
Purpose of the Study:
- To investigate the functional link between Hh signaling and αvβ6 integrin in cancer.
- To explore the mechanisms regulating αvβ6 expression in response to Hh pathway modulation.
Main Methods:
- Generated BCC models overexpressing Gli1 in keratinocytes.
- Investigated αvβ6 expression changes upon Gli1 suppression.
- Utilized in vitro cell culture and human clinical samples (BCC and pancreatic cancer).
Main Results:
- Suppressing Gli1 (a key Hh pathway mediator) significantly increased αvβ6 integrin expression.
- Increased αvβ6 promoted tumor cell motility and myofibroblast differentiation via TGF-β1.
- Gli1 was found to inhibit αvβ6 expression by suppressing TGF-β1/Smad2/3 signaling.
- An inverse correlation between Gli1 and αvβ6 expression was observed in human BCC and pancreatic cancer samples.
Conclusions:
- Hh pathway targeting can paradoxically up-regulate αvβ6 integrin, promoting pro-tumorigenic functions.
- A feedback loop exists where Gli1 suppresses αvβ6, and αvβ6 promotes invasion.
- Findings have clinical implications for managing BCC recurrence and secondary malignancies after Hh inhibitor therapy.
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