SMYD3: An Oncogenic Driver Targeting Epigenetic Regulation and Signaling Pathways

Cancers

Cinzia Bottino¹  Giuseppina Caretti¹  Alessia Peserico²  Cristiano Simone³ 

[1] Department of Biosciences, Università degli Studi Milano, Via Celoria 26, 20133 Milan, Italy;Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy;Medical Genetics, National Institute of Gastroenterology, ‘S. de Bellis’ Research Hospital, Via Turi 27, Castellana Grotte, 70013 Bari, Italy;

关键词: smyd3;    kmt;    epigenetic inhibitors;    lysine methylation;   

DOI  :  10.3390/cancers12010142

来源: DOAJ

【 摘 要 】

SMYD3 is a member of the SMYD lysine methylase family and plays an important role in the methylation of various histone and non-histone targets. Aberrant SMYD3 expression contributes to carcinogenesis and SMYD3 upregulation was proposed as a prognostic marker in various solid cancers. Here we summarize SMYD3-mediated regulatory mechanisms, which are implicated in the pathophysiology of cancer, as drivers of distinct oncogenic pathways. We describe SMYD3-dependent mechanisms affecting cancer progression, highlighting SMYD3 interplay with proteins and RNAs involved in the regulation of cancer cell proliferation, migration and invasion. We also address the effectiveness and mechanisms of action for the currently available SMYD3 inhibitors. The findings analyzed herein demonstrate that a complex network of SMYD3-mediated cytoplasmic and nuclear interactions promote oncogenesis across different cancer types. These evidences depict SMYD3 as a modulator of the transcriptional response and of key signaling pathways, orchestrating multiple oncogenic inputs and ultimately, promoting transcriptional reprogramming and tumor transformation. Further insights into the oncogenic role of SMYD3 and its targeting of different synergistic oncogenic signals may be beneficial for effective cancer treatment.

【 授权许可】

Unknown