Aberrant expression of JNK-associated leucine-zipper protein, JLP, promotes accelerated growth of ovarian cancer

Autor: Danny N. Dhanasekaran, Muralidharan Jayaraman, Rohini Gomathinayagam, E. Premkumar Reddy, Mingda Yan, Sanam Husain, Jinsong Liu, Ji Hee Ha, Priyabrata Mukherjee, Yong Sang Song
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Pathology
endocrine system diseases
Proto-Oncogene Proteins c-jun
medicine.medical_treatment
SPAG9
scaffold
Small hairpin RNA
chemistry.chemical_compound
Mice
0302 clinical medicine
Cell Movement
Lysophosphatidic acid
Ovarian Neoplasms
3. Good health
Tumor Burden
Gene Expression Regulation
Neoplastic
ovarian cancer
Oncology
030220 oncology & carcinogenesis
Gene Knockdown Techniques
Heterografts
Female
Research Paper
Protein Binding
Leucine zipper
medicine.medical_specialty
JLP
Models
Biological
03 medical and health sciences
Cell Line
Tumor
medicine
Animals
Humans
Clonogenic assay
Adaptor Proteins
Signal Transducing
Cell Proliferation
business.industry
Growth factor
Cancer
medicine.disease
Disease Models
Animal
030104 developmental biology
chemistry
Cancer research
Ectopic expression
JNK
Lysophospholipids
Ovarian cancer
business
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: // Ji Hee Ha 1, 2, * , Mingda Yan 1, * , Rohini Gomathinayagam 1, 2 , Muralidharan Jayaraman 1, 2 , Sanam Husain 3 , Jinsong Liu 4 , Priyabrata Mukherjee 1, 3 , E. Premkumar Reddy 5 , Yong Sang Song 6 , Danny N. Dhanasekaran 1, 2 1 Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA 2 Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA 3 Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA 4 The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA 5 Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA 6 Cancer Research Institute, Seoul National University, College of Medicine, Seoul 151-921, Korea * These authors contributed equally to this work Correspondence to: Danny N. Dhanasekaran, email: danny-dhanasekaran@ouhsc.edu Keywords: JLP, JNK, scaffold, ovarian cancer, SPAG9 Received: July 27, 2016 Accepted: September 10, 2016 Published: September 16, 2016 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 J NK-associated L eucine zipper P rotein (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.
Databáze: OpenAIRE
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