Research Papers:

Negative correlation of ITCH E3 ubiquitin ligase and miRNA-106b dictates metastatic progression in pancreatic cancer

Zhu-lin Luo, Hui-jun Luo, Chen Fang, Long Cheng, Zhu Huang, Ruiwu Dai, Kun Li, Fu-zhou Tian, Tao Wang and Li-jun Tang _

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Oncotarget. 2016; 7:1477-1485. https://doi.org/10.18632/oncotarget.6395

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Zhu-lin Luo1,*, Hui-jun Luo2,*, Chen Fang3,*, Long Cheng1,*, Zhu Huang1, Ruiwu Dai1, Kun Li4, Fu-zhou Tian1, Tao Wang1, Li-jun Tang1

1Department of General Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China

2Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA

3Chengdu Military Institute for Drug and Instrument Control, Chengdu, Sichuan 610020, P. R. China

4Medical Central Laboratory, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P. R. China

*These authors contributed equally to this work

Correspondence to:

Li-jun Tang, e-mail: [email protected]

Tao Wang, e-mail: [email protected]

Keywords: ITCH, miR-106b, pancreatic cancer, YAP, metastasis

Received: April 24, 2015     Accepted: November 14, 2015     Published: November 26, 2015


Pancreatic cancer is one of the major malignancies and cause for mortality across the world, with recurrence and metastatic progression remaining the single largest cause of pancreatic cancer mortality. Hence it is imperative to develop novel biomarkers of pancreatic cancer prognosis. The E3 ubiquitin ligase ITCH has been previously reported to inhibit the tumor suppressive Hippo signaling by suppressing LATS1/2 in breast cancer and chronic lymphocytic leukemia. However, the role of ITCH in pancreatic cancer progression has not been described. Here we report that ITCH transcript and protein expression mimic metastatic trait in pancreatic cancer patients and cell lines. Loss-of-function studies of ITCH showed that the gene product is responsible for inducing metastasis in vivo. We furthermore show that hsa-miR-106b, which itself is down regulated in metastatic pancreatic cancer, directly interacts and inhibit ITCH expression. ITCH and hsa-miR-106b are thus potential biomarkers for pancreatic cancer prognosis.

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