MEK2 is a critical modulating mechanism to down‐regulate GCIP stability and function in cancer cells

Abstract

Loss of tumor suppressor activity and upregulation of oncogenic pathways simultaneously contribute to tumorigenesis. Expression of the tumor suppressor, GCIP (Grap2-and cyclin D1-interacting protein), is usually reduced or lost in advanced cancers, as seen in both mouse tumor models and human cancer patients. However, no previous study has examined how cancer cells down-regulate GCIP expression.In this study, we first validate the tumor suppressive function of GCIP using clinical gastric cancer tissues and online database analysis. We then reveal a novel mechanism whereby MEK2 directly interacts with and phosphorylates GCIP at its Ser313 and Ser356 residues to promote the turnover of GCIP by ubiquitin-mediated proteasomal degradation. We also reveal that decreased GCIP stability enhances cell proliferation and promotes cancer cell migration and invasion. Taken together, these findings provide a more comprehensive view of GCIP in tumorigenesis and suggest that the oncogenic MEK/ERK signaling pathway negatively regulates the protein level of GCIP to promote cell proliferation and migration. K E Y W O R D SGCIP, MEK2, tumor suppressor, ubiquitination

CCNDBP1, a Prognostic Marker Regulated by DNA Methylation, Inhibits Aggressive Behavior in Dedifferentiated Liposarcoma via Repressing Epithelial Mesenchymal Transition

“…The ROC curve indicated that the sensitivity to predict the progression of DDL patients was 90.91%, but the specificity was poor at only 57.14%, with the cutoff of the AOD value for CCNDBP1 IHC staining was >0.1950. Previous studies reported that CCNDBP1 was correlated with the occurrence and development of breast cancer, colon cancer, liver cancer, non-small cell lung cancer, osteosarcoma, and gastric cancer (9,(23)(24)(25)(26)(27)(28)(29). Therefore, the expression of CCNDBP1 might not be tumor-specific.…”

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Capsaicin Potentiates Anticancer Drug Efficacy Through Autophagy-Mediated Ribophorin II Downregulation and Necroptosis in Oral Squamous Cell Carcinoma Cells

“…Cell proliferation was monitored by measuring cell impedance, and the normalized cell index was determined as previously described (Lin et al, 2018). Data acquisition and analysis were performed with the RTCA software (version 2.0) as described previously (Liang et al, 2020).…”

Phosphorylation Sites in Protein Kinases and Phosphatases Regulated by Formyl Peptide Receptor 2 Signaling

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