4.7 Review

The emerging role of the KCTD proteins in cancer

Journal

CELL COMMUNICATION AND SIGNALING
Volume 19, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12964-021-00737-8

Keywords

KCTD family; BTB domain; Cancer; Oncogene; Tumor suppressor; KCASH family; KCTD15; Cul3; Ubiquitination

Categories

Funding

  1. Italian Ministry of University and Research, PRIN projects
  2. Sapienza Research Grant year 2015
  3. Sapienza Research Grant year 2017
  4. Sapienza Research Grant 2019

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The KCTD protein family plays important roles in neurological disorders, obesity, and cancer, with many members still not fully characterized. Research suggests that KCTD members may be potential therapeutic targets or diagnostic/prognostic markers, highlighting the need for further investigation into their roles in tumorigenesis. These factors demonstrate the complexity and significance of KCTD proteins in cancer and other diseases.
The human family of Potassium (K+) Channel Tetramerization Domain (KCTD) proteins counts 25 members, and a significant number of them are still only partially characterized. While some of the KCTDs have been linked to neurological disorders or obesity, a growing tally of KCTDs are being associated with cancer hallmarks or involved in the modulation of specific oncogenic pathways. Indeed, the potential relevance of the variegate KCTD family in cancer warrants an updated picture of the current knowledge and highlights the need for further research on KCTD members as either putative therapeutic targets, or diagnostic/prognostic markers. Homology between family members, capability to participate in ubiquitination and degradation of different protein targets, ability to heterodimerize between members, role played in the main signalling pathways involved in development and cancer, are all factors that need to be considered in the search for new key players in tumorigenesis. In this review we summarize the recent published evidence on KCTD members' involvement in cancer. Furthermore, by integrating this information with data extrapolated from public databases that suggest new potential associations with cancers, we hypothesize that the number of KCTD family members involved in tumorigenesis (either as positive or negative modulator) may be bigger than so far demonstrated.

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