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APPL proteins promote TGF beta-induced nuclear transport of the TGF beta type I receptor intracellular domain
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- Song, Jie (author)
- Umeå universitet,Patologi,Umea Univ, Med Biosci, Umea, Sweden.
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- Mu, Yabing (author)
- Umeå universitet,Patologi,Umea Univ, Med Biosci, Umea, Sweden.
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- Li, Chunyan (author)
- Jilin Univ, Stomatol Hosp, Implant Ctr, Changchun 130023, Peoples R China.
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- (creator_code:org_t)
- 2015-11-18
- 2016
- English.
- In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:1, s. 279-292
- Journal article (peer-reviewed)
Abstract
Subject headings
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- The multifunctional cytokine transforming growth factor-beta (TGF beta) is produced by several types of cancers, including prostate cancer, and promote tumour progression in autocrine and paracrine manners. In response to ligand binding, the TGF beta type I receptor (T beta RI) activates Smad and non-Smad signalling pathways. The ubiquitin-ligase tumour necrosis factor receptor-associated factor 6 (TRAF6) was recently linked to regulate intramembrane proteolytic cleavage of the T beta RI in cancer cells. Subsequently, the intracellular domain (ICD) of T beta RI enters in an unknown manner into the nucleus, where it promotes the transcription of pro-invasive genes, such as MMP2 and MMP9. Here we show that the endocytic adaptor molecules APPL1 and APPL2 are required for TGF beta-induced nuclear translocation of T beta RI-ICD and for cancer cell invasiveness of human prostate and breast cancer cell lines. Moreover, APPL proteins were found to be expressed at high levels in aggressive prostate cancer tissues, and to be associated with T beta RI in a TRAF6-dependent manner. Our results suggest that the APPL-T beta RI complex promotes prostate tumour progression, and may serve as a prognostic marker.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- APPL proteins
- prostate cancer
- signal transduction
- tumour necrosis factor receptor-associated factor 6
- transforming growth factor beta
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- art (subject category)
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- Oncotarget
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- Umeå University
- Uppsala University
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