Dataset Information

Usnic acid target CRYAB phosphorylation to induce ferroptosis

ABSTRACT: This study elucidates the critical role of CRYAB phosphorylation in driving the progression of liver metastasis in colorectal cancer, and validates that usnic acid exerts anti-metastatic activity by modulating this post-translational modification. Mechanistically, in addition to its established pro-apoptotic function, usnic acid triggers ferroptosis via suppressing CRYAB phosphorylation at the S59 site. These results construct a mechanistic basis for usnic acid as a promising therapeutic candidate against metastatic colorectal cancer, underscoring the translational potential of targeting CRYAB phosphorylation and ferroptosis for the clinical intervention of colorectal cancer liver metastases.

ORGANISM(S): Homo Sapiens

SUBMITTER: Jinlai Wei

PROVIDER: PXD075743 | iProX | Tue Mar 17 00:00:00 GMT 2026

REPOSITORIES: iProX

ACCESS DATA

Similar Datasets

Project description:Colorectal cancer (CRC) is one of the most lethal cancers when it progresses to the advanced/metastatic stage. Treatment options for refractory metastatic colorectal cancer (mCRC) are limited. Therefore, there is an urgent need to develop effective treatment methods for metastatic colorectal cancer. In this study, we screened a library of small molecules for inhibitors of CRC recurrence using CRC cell lines and patient-derived organoids (PDOs) from metastatic, heavily pretreated CRC. The in vivo efficacy of LS-1-2 was evaluated in the HCT116 and the resistant HCT8 cell lines, patient-derived xenografts(PDXs) including refractory mCRC, and a liver metastasis mouse model. Biotin pull-down and liquid chromatography tandem-mass spectrometry (LC-MS/MS) were performed to identify proteins that interact with LS-1-2. The genome-wide gene expression and quantitative phosphoproteomic analyses were performed to determine the signaling pathway involved in LS-1-2. Molecular docking, molecular dynamics analysis and cellular thermal shift assays were used to predict and validate the binding sites of LS-1-2 on non-muscle Myosin IIA (NMHC IIA). Our results showed that LS-1-2 exhibited broad antiproliferative effects on a series of CRC cell lines and PDOs. The in vivo anti-tumor efficacy of LS-1-2 was demonstrated across cell line- and patient-derived xenografts and in the liver metastatic CRC model. NMHC IIA was identified as a direct target of LS-1-2, and LS-1-2 competitively inhibited the phosphorylation of NMHC IIA at S1943 and S1714 by CK2. NMHC IIA phosphorylation promoted CRC cell proliferation and invasion, which was reduced by LS-1-2. NMHC IIA phosphorylation-mediated YAP activity induced activation of AKT and inactivation of FOXO3a and was suppressed by LS-1-2. In conclusion, our findings suggest that NMHC IIA phosphorylation can be used as a potential molecular target in CRC metastasis, and that targeting NMHC IIA phosphorylation by LS-1-2 may be a promising strategy for the treatment and prevention of CRC metastasis.

Dataset Information

Usnic acid target CRYAB phosphorylation to induce ferroptosis

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets