title: Myc suppresses tumor invasion and cell migration by inhibiting JNK signaling.
abstract: Tumor metastasis, but not primary overgrowth, is the leading cause of mortality for cancer patients. During the past decade, Drosophila melanogaster has been well-accepted as an excellent model to address the intrinsic mechanism of different aspects of cancer progression, ranging from tumor initiation to metastasis. In a genetic screen performed in Drosophila, aiming to find novel modulators of tumor invasion, we identified the oncoprotein Myc as a negative regulator. While expression of Myc dramatically blocks tumor invasion and cell migration, loss of Myc promotes cell migration in vivo. The activity of Myc is further enhanced by the co-expression of its transcription partner Max. Mechanistically, we found Myc/Max directly upregulates the transcription of puc, which encodes an inhibitor of JNK signaling crucial for tumor invasion and cell migration. Furthermore, we demonstrated that human cMyc potently suppresses JNK-dependent cell invasion and migration in both Drosophila and lung adenocarcinoma cell lines. These findings provide novel molecular insights into Myc-mediated cancer progression and raise the noteworthy problem in therapeutic strategies as inhibiting Myc might conversely accelerate tumor metastasis.
authors.affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.affiliation: Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Clinical Translational Research Center, Shanghai Pulmonary Hospital, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: F
authors.identifier: 0000-0003-4068-3726
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Institute of Intervention Vessel, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Xue
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D004331:Drosophila melanogaster; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D048670:MAP Kinase Kinase 4