title: Hedgehog pathway regulators influence cervical cancer cell proliferation, survival and migration.
abstract: Human papillomavirus (HPV) infection is considered to be a primary hit that causes cervical cancer. However, infection with this agent, although needed, is not sufficient for a cancer to develop. Additional cellular changes are required to complement the action of HPV, but the precise nature of these changes is not clear. Here, we studied the function of the Hedgehog (Hh) signaling pathway in cervical cancer. The Hh pathway can have a role in a number of cancers, including those of liver, lung and digestive tract. We found that components of the Hh pathway are expressed in several cervical cancer cell lines, indicating that there could exists an autocrine Hh signaling loop in these cells. Inhibition of Hh signaling reduces proliferation and survival of the cervical cancer cells and induces their apoptosis as seen by the up-regulation of the pro-apoptotic protein cleaved caspase 3. Our results indicate that Hh signaling is not induced directly by HPV-encoded proteins but rather that Hh-activating mutations are selected in cells initially immortalized by HPV. Sonic Hedgehog (Shh) ligand induces proliferation and promotes migration of the cervical cancer cells studied. Together, these results indicate pro-survival and protective roles of an activated Hh signaling pathway in cervical cancer-derived cells, and suggest that inhibition of this pathway may be a therapeutic option in fighting cervical cancer.
authors: Ecole Polytechnique Fédérale Lausanne (EPFL), Department of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), 1015 Lausanne, Switzerland.
authors: Ivana
authors: I
authors: Samarzija
authors: Peter
authors: P
authors: Beard
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D006367:HeLa Cells; D053823:Hedgehog Proteins / Q000378:metabolism*; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D008024:Ligands; D011725:Pyridines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology
chemical_list: C551027:GANT 61; D053823:Hedgehog Proteins; D008024:Ligands; D011725:Pyridines; D011743:Pyrimidines; D053148:Caspase 3