Id2, Id3 and Id4 overcome a Smad7-mediated block in tumorigenesis, generating TGF-β-independent melanoma

Carcinogenesis
Kyle A DiVitoDean S Rosenthal

Abstract

The role for the inhibitors of differentiation (Ids) proteins in melanomagenesis has been poorly explored. In other cell types, Ids have been shown to contribute to cell proliferation, migration and angiogenesis and, along with a number of other genes, are direct downstream targets of the transforming growth factor (TGF)-β pathway. Expression of Smad7, which suppress TGF-β signaling, or synthetic TGF-β inhibitors, was shown to potently suppress melanomagenesis. We found that endogenous Id2, Id3 and Id4 expression was elevated in 1205Lu versus 1205Lu cells constitutively expressing Smad7, indicating Ids may play a role in melanomagenesis. Therefore, the effects of Tet-inducible expression of Id2, Id3 or Id4 along with Smad7 in TGF-β-dependent 1205Lu human melanoma cells were explored in vitro and in vivo. 1205Lu cells formed subcutaneous tumors in athymic mice, whereas cells expressing Smad7 failed to form tumors. However, 1205Lu cells expressing Smad7 along with doxycycline-induced Id2, Id3 or Id4 were able to overcome the potent tumorigenic block mediated by S7, to varying degrees. Conversely, Id small interfering RNA knockdown suppressed anchorage-independent growth of melanoma. Histology of tumors from 1205Lu cells expressin...Continue Reading

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Citations

Feb 20, 2015·Cancer Medicine·You-Shin ChenDean S Rosenthal
Sep 3, 2016·Seminars in Cancer Biology·Gaia CantelliVictoria Sanz-Moreno
Mar 5, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jia LiYuan Zhuang
Oct 10, 2018·Scientific Reports·Ruo-Lin WuJonathan P Sleeman
Dec 26, 2018·Advanced Science·Jialang ZhuangYuanqing Zhang
Jun 2, 2017·Biomaterials·Kyle A DiVitoAndré A Adams
Jul 2, 2021·Nucleic Acids Research·Mengfan TangJunjie Chen
Sep 4, 2021·Nature Cell Biology·Rachel L BeloteRobert L Judson-Torres

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