Oncotarget

Research Papers:

IGF2BP3-mediated translation in cell protrusions promotes cell invasiveness and metastasis of pancreatic cancer

Keisuke Taniuchi _, Mutsuo Furihata, Kazuhiro Hanazaki, Motoaki Saito and Toshiji Saibara

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Oncotarget. 2014; 5:6832-6845. https://doi.org/10.18632/oncotarget.2257

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Abstract

Keisuke Taniuchi1, Mutsuo Furihata2, Kazuhiro Hanazaki3, Motoaki Saito1 and Toshiji Saibara4

1 Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan

2 Department of Pathology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan

3 Department of Surgery, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan

4 Department of Gastroenterology and Hepatology, Kochi Medical School, Kochi University, Nankoku, Kochi, Japan

Correspondence:

Keisuke Taniuchi, email:

Keywords: RNA-binding protein, pancreatic cancer, cell invasion and metastasis, stress granule, local translation, cell protrusion

Received: June 10, 2014 Accepted: July 24, 2014 Published: July 25, 2014

Abstract

Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that IGF2BP3 promoted the invasiveness and metastasis of pancreatic cancers through locally translated IGF2BP3-bound transcripts. In neural cells, transcripts sorted into cytoplasmic RNA granules are transported to dendrites and translated in these dendrites, thereby mediating long-term synaptic plasticity; however, such cytoplasmic RNA granules are not known to contribute to the progression of pancreatic cancer. We show evidence that IGF2BP3 and IGF2BP3-bound transcripts are localized in cytoplasmic RNA granules that accumulate in membrane protrusions of pancreatic cancer cells. Specific IGF2BP3-bound transcripts—ARF6 and ARHGEF4—that are preferentially translated in membrane protrusions induce further formation of membrane protrusions; consequently, IGF2BP3 promotes cell invasiveness and tumor metastasis. Our results provide insight into the link between regulation of localized translation in cell protrusions and the invasiveness and metastasis of pancreatic cancers. New therapies that prevent local translation in cell protrusions may hold significant clinical promise.


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