CRIP1 Drives Ovarian Cancer Progression by Stabilizing KRAS in Experimental Models

Cysteine-Rich Protein 1 (CRIP1) expression is significantly upregulated in ovarian cancer tissues compared to adjacent normal tissues, and high expression levels correlate with poor patient prognosis.

To investigate the role of CRIP1 in ovarian cancer pathogenesis, researchers examined public databases and clinical ovarian cancer tissue samples. In vitro investigations utilized the ovarian cancer cell lines HEY and SKOV3, measuring gene and protein expression through quantitative reverse transcription polymerase chain reaction, Western blotting, immunohistochemistry, and immunofluorescence.

Functional cellular assays revealed that CRIP1 overexpression enhanced ovarian cancer cell proliferation, migration, and invasion, whereas CRIP1 knockdown suppressed these malignant behaviors. Cell proliferation was measured using CCK-8 and EDU assays, while migratory and invasive capacities were quantified using wound healing and Transwell assays.

Mechanistic analyses using co-immunoprecipitation confirmed a protein-protein interaction among CRIP1, KRAS, and USP7. Overexpressing CRIP1 increased the amount of USP7-bound KRAS and elevated total KRAS protein levels, while treatment with the USP7 inhibitor P5091 destabilized KRAS. Furthermore, knocking down KRAS reversed the increases in cell proliferation, migration, and invasion induced by CRIP1 overexpression.

Validation in xenograft mouse models demonstrated that CRIP1 overexpression significantly accelerated ovarian cancer progression in vivo. Based on these cellular and animal model results, the authors concluded that CRIP1 promotes progression by mediating the KRAS-USP7 interaction to stabilize KRAS, identifying the protein as a potential therapeutic target.

In addressing ovarian cancer as a leading cause of gynecological cancer mortality, the study emphasized the necessity of uncovering deeper molecular mechanisms that govern disease pathogenesis.

Subject of Research: Molecular mechanism of CRIP1 in ovarian cancer progression and KRAS stabilization

Article Title: CRIP1 Promotes Ovarian Cancer Progression by Mediating the KRAS-USP7 Interaction and Stabilizing KRAS

Article References: Zhan, Q., Zhuang, Y., Wang, H., Wu, Z., Zhu, T., Tian, M., Li, L., Du, Y., & Chen, H. (2026). CRIP1 Promotes Ovarian Cancer Progression by Mediating the KRAS-USP7 Interaction and Stabilizing KRAS. Reproductive Sciences. https://doi.org/10.1007/s43032-026-02224-2

Image Credits: AI Generated

DOI: 10.1007/s43032-026-02224-2

Keywords: ovarian cancer, CRIP1, KRAS, USP7, deubiquitinase, oncology, xenograft models, protein stabilization, Promotes, Ovarian, Cancer, Progression