title: Aberrant expression of JNK-associated leucine-zipper protein, JLP, promotes accelerated growth of ovarian cancer.
abstract: Ovarian cancer is the most fatal gynecologic cancer with poor prognosis. Etiological factors underlying ovarian cancer genesis and progression are poorly understood. Previously, we have shown that JNK-associated Leucine zipper Protein (JLP), promotes oncogenic signaling. Investigating the role of JLP in ovarian cancer, our present study indicates that JLP is overexpressed in ovarian cancer tissue and ovarian cancer cells. Transient overexpression of JLP promotes proliferation and invasive migration of ovarian cancer cells. In addition, ectopic expression of JLP confers long-term survival and clonogenic potential to normal fallopian tube-derived epithelial cells. Coimmunoprecipitation and colocalization analyses demonstrate the in vivo interaction of JLP and JNK, which is stimulated by lysophosphatidic acid (LPA), an oncogenic lipid growth factor in ovarian cancer. We also show that LPA stimulates the translocation of JLP-JNK complex to the perinuclear region of SKOV3-ip cells. JLP-knockdown using shRNA abrogates LPA-stimulated activation of JNK as well as LPA-stimulated proliferation and invasive migration of SKOV3-ip cells. Studies using ovarian cancer xenograft mouse model indicate that the mice bearing JLP-silenced xenografts exhibits reduced tumor volume. Analysis of the xenograft tumor tissues indicate a reduction in the levels of JLP, JNK, phosphorylated-JNK, c-Jun and phosphorylated-c-Jun in JLP-silenced xenografts, thereby correlating the attenuated JLP-JNK signaling node with suppressed tumor growth. Thus, our results identify a critical role for JLP-signaling axis in ovarian cancer and provide evidence that targeting this signaling node could provide a new avenue for therapy.
authors.affiliation: Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.|Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Ha
authors.affiliation: Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Mingda
authors.initials: M
authors.lastname: Yan
authors.affiliation: Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.|Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Rohini
authors.initials: R
authors.lastname: Gomathinayagam
authors.affiliation: Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.|Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Muralidharan
authors.initials: M
authors.lastname: Jayaraman
authors.affiliation: Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Sanam
authors.initials: S
authors.lastname: Husain
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.|Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Priyabrata
authors.initials: P
authors.lastname: Mukherjee
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: E Premkumar
authors.initials: EP
authors.lastname: Reddy
authors.affiliation: Cancer Research Institute, Seoul National University, College of Medicine, Seoul 151-921, Korea.
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Song
authors.affiliation: Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.|Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Danny N
authors.initials: DN
authors.lastname: Dhanasekaran
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008246:Lysophospholipids; D016755:Proto-Oncogene Proteins c-jun; C111047:SPAG9 protein, human; C032881:lysophosphatidic acid
keywords: JLP; JNK; SPAG9; ovarian cancer; scaffold