title: Leptin enhances migration of human papillary thyroid cancer cells through the PI3K/AKT and MEK/ERK signaling pathways.
abstract: The incidence of thyroid cancer has remarkably increased in recent years. Epidemiologic data suggest that obesity is associated with an increased incidence of several types of malignancies, including thyroid cancer. Leptin, an adipocyte-derived cytokine, has been shown to be involved in cancer development and progression. We previously demonstrated that papillary thyroid cancer expressing leptin receptor and/or leptin has a higher incidence of lymph node metastasis. In this study, we investigated the effects of leptin on cell migration in K1 and B-CPAP papillary thyroid cancer cells. Expression of leptin receptor was observed in both cell lines. Leptin enhanced the migratory activity significantly in a dose-dependent manner. We showed that leptin induced AKT and extracellular signal-regulated kinase (ERK) phosphorylation. Inhibition of phosphatidylinositol 3-kinase and ERK activation using pharmacological inhibitors effectively blocked leptin-induced migration of K1 and B-CPAP cells. Taken together, this study provides new mechanistic evidence for a role of leptin in the regulation of papillary thyroid cancer progression by stimulating tumor cell migration.
authors.affiliation: Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan, ROC.
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Cheng
authors.forename: Pen-Hui
authors.initials: PH
authors.lastname: Yin
authors.forename: Yi-Chiung
authors.initials: YC
authors.lastname: Hsu
authors.forename: Yuan-Ching
authors.initials: YC
authors.lastname: Chang
authors.forename: Shih-Yuan
authors.initials: SY
authors.lastname: Huang
authors.forename: Jie-Jen
authors.initials: JJ
authors.lastname: Lee
authors.forename: Chin-Wen
authors.initials: CW
authors.lastname: Chi
mesh_terms: D002277:Carcinoma; D002291:Carcinoma, Papillary / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D054411:Receptors, Leptin / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases