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.

journal_name

Oncogene

journal_title

Oncogene

authors

Ma X,Huang J,Tian Y,Chen Y,Yang Y,Zhang X,Zhang F,Xue L

doi

10.1038/onc.2016.463

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

3159-3167

issue

22

eissn

0950-9232

issn

1476-5594

pii

onc2016463

journal_volume

36

pub_type

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