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The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human Cancer

Department of Pathology, Comprehensive Cancer Center, University of Alabama at Birmingham,WTI320D, 1824 6th Avenue South, Birmingham, AL 35233, USA
Author to whom correspondence should be addressed.
Academic Editor: Hui-Wen Lo
Cancers 2015, 7(3), 1333-1348;
Received: 25 May 2015 / Revised: 10 July 2015 / Accepted: 14 July 2015 / Published: 21 July 2015
Defined cellular mechanisms have evolved that recognize and repair DNA to protect the integrity of its structure and sequence when encountering assaults from endogenous and exogenous sources. There are five major DNA repair pathways: mismatch repair, nucleotide excision repair, direct repair, base excision repair and DNA double strand break repair (including non-homologous end joining and homologous recombination repair). Aberrant activation of the Hedgehog (Hh) signaling pathway is a feature of many cancer types. The Hh pathway has been documented to be indispensable for epithelial-mesenchymal transition, invasion and metastasis, cancer stemness, and chemoresistance. The functional transcription activators of the Hh pathway include the GLI proteins. Inhibition of the activity of GLI can interfere with almost all DNA repair types in human cancer, indicating that Hh/GLI functions may play an important role in enabling tumor cells to survive lethal types of DNA damage induced by chemotherapy and radiotherapy. Thus, Hh signaling presents an important therapeutic target to overcome DNA repair-enabled multi-drug resistance and consequently increase chemotherapeutic response in the treatment of cancer. View Full-Text
Keywords: Hedgehog; cancer; DNA repair; drug resistance Hedgehog; cancer; DNA repair; drug resistance
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Meng, E.; Hanna, A.; Samant, R.S.; Shevde, L.A. The Impact of Hedgehog Signaling Pathway on DNA Repair Mechanisms in Human Cancer. Cancers 2015, 7, 1333-1348.

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