title: TNFR1 Regulates Ovarian Cancer Cell Tumorigenicity Through PIK3CB-p110Beta.
abstract: Studies have shown that TNFR1 is a key factor in the tumor microenvironment that is dependent on the TNF-α-initiated cascade for tumorigenesis. In this present study, we found that TNFR1 is over-expressed in ovarian cancer, which is relevant to both clinical survival and disease free status. Knockdown of TNFR1 dramatically attenuates malignant phenotypes, including proliferation and colony growth in soft agar, as well as glycolysis in ovarian cancer cells. Unexpectedly, knocking down TNFR1 blocks EGF-induced p-AKT and p-p70S6K expression and EGF-induced cell transformation through PIK3-p110beta rather than p110alpha expression. Taken together, our data provide evidence that TNFR1 plays a critical role in ovarian cancer and show that the EGF induced signaling pathway is independent of the TNF-α triggering cascade signal. Therefore, TNFR1 may serve as a prognostic molecule in ovarian cancer.
authors.forename: C
authors.initials: C
authors.lastname: Peng
authors.forename: J
authors.initials: J
authors.lastname: Su
authors.forename: W
authors.initials: W
authors.lastname: Zeng
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University, Xiangya Road #87, Changsha, Hunan 410008, China. chenxiangck@gmail.com.
authors.forename: X
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D058534:Class I Phosphatidylinositol 3-Kinases; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000096:biosynthesis; D051379:Mice; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011379:Prognosis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D047368:Tumor Burden / Q000235:genetics
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; D019344:Lactic Acid; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C497132:PIK3CB protein, human; D005947:Glucose