The Oncosuppressive Properties of KCTD1: Its Role in Cell Growth and Mobility

The KCTD protein family is traditionally regarded as proteins that play key roles in neuro-logical physiopathology. However, new studies are increasingly demonstrating their involvement in many other biological processes, including cancers. This is particularly evident for KCTD proteins not involved in protein ubiquitination and degradation, such as KCTD1. We explored the role of KCTD1 in colorectal cancer by knocking down this protein in the human colon adenocarcinoma cell line, SW480. We re-assessed its ability to downregulate (3-catenin, a central actor in the WNT/(3-catenin signalling pathway. Interestingly, opposite effects are observed when the protein is upregulated in CACO2 colorectal cancer cells. Moreover, interrogation of the TCGA database indicates that KCTD1 downregulation is associated with (3-catenin overexpression in colorectal cancer patients. Indeed, knocking down KCTD1 in SW480 cells led to a significant increase in their motility and stemness, two important tumorigenesis traits, suggesting an oncosuppressor role for KCTD1. It is worth noting that similar effects are induced on colorectal cancer cells by the misregulation of KCTD12, a protein that is distantly related to KCTD1. The presented results further expand the spectrum of KCTD1 involvement in apparently unrelated physiopathological processes. The similar effects produced on colorectal cancer cell lines by KCTD1 and KCTD12 suggest novel, previously unreported analogous activities among members of the KCTD protein family.

Automated summary

The KCTD protein family has been traditionally recognized as playing important roles in neurological physiopathology, but recent studies have shown their involvement in various biological processes, including cancers. This study focused on KCTD1 and its role in colorectal cancer. Knocking down KCTD1 in SW480 cells led to significant effects on their motility and stemness, indicating an oncosuppressor role for this protein. Similar effects were also observed with KCTD12 misregulation. These results expand the understanding of KCTD1's involvement in different physiological and pathological processes and suggest analogous activities among KCTD protein family members.