title: Stem cell factor/c-kit signaling enhances invasion of pancreatic cancer cells via HIF-1α under normoxic condition.
abstract: The SCF/c-kit signaling plays an important role in invasion of c-kit-expressing tumor cells, however, the molecular mechanisms have not been studied yet. Using a pancreatic cancer model, we demonstrate that SCF/c-kit binding up-regulates the expression of invasion-related genes through the accumulation of HIF-1α. Furthermore, the expression of HIF-1α induced by SCF is not dependent on the oxygen level, but rather on both the PI3K/Akt and Ras/MEK/ERK signaling pathways. In conclusion, under normoxic conditions, SCF/c-kit binding increases expression of HIF-1α through the PI3K/Akt and Ras/MEK/ERK pathways, and the accumulation of HIF-1α up-regulates expression of invasion-related genes that augment the invasiveness of pancreatic cancer, a fatal cancer. Therefore, our results suggest that the inhibition of both c-kit and HIF-1α may be an effective strategy for pancreatic cancer therapy.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Ma
authors.forename: Hengtong
authors.initials: H
authors.lastname: Hu
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Junhui
authors.initials: J
authors.lastname: Li
authors.forename: Guodong
authors.initials: G
authors.lastname: Ma
authors.forename: Kruttika
authors.initials: K
authors.lastname: Bhat
authors.forename: Erxi
authors.initials: E
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010100:Oxygen / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit; D010100:Oxygen