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MAD2 activates IGF1R/PI3K/AKT pathway and promotes cholangiocarcinoma progression by interfering USP44/LIMA1 complex
Summary
This article discusses the role of mitotic arrest deficient 2 like 1 (MAD2/MAD2L1) in the progression of cholangiocarcinoma (CCA). The authors found that higher levels of MAD2 facilitated CCA progression and induced lymphatic metastasis, and interfered with the binding of USP44 to LIMA1. The data combined with eleven CCA patient models showed that high-MAD2 inhibited tumor necrosis and diminished the inhibition of cell viability after treatment with gemcitabine-based regimens. Immunohistochemistry analysis of tissue microarray for CCA patients revealed that high-MAD2, low-USP44 or low-LIMA1 levels are correlated with worse survival for patients. This suggests that MAD2 might be an excellent indicator in prognosis analysis and chemotherapy guidance for CCA patients.
Q&As
What is the role and mechanism of MAD2 in cholangiocarcinoma progression?
MAD2 facilitates cholangiocarcinoma progression and induces lymphatic metastasis dependent on USP44/LIMA1/PI3K/AKT pathway.
How does MAD2 interfere with the USP44/LIMA1 complex?
MAD2 interferes with the binding of USP44 to LIMA1 by sequestrating more USP44 in nuclei, causing impaired formation of USP44/LIMA1 complex and enhanced LIMA1 K48 (Lys48)-linked ubiquitination.
What is the effect of high-MAD2 on tumor necrosis and cell viability in CCA?
High-MAD2 inhibits tumor necrosis and diminishes the inhibition of cell viability after treated with gemcitabine-based regimens.
How does MAD2 expression correlate with patient prognosis in CCA?
High-MAD2, low-USP44 or low-LIMA1 level are correlated with worse survival for patients.
What are the implications of MAD2 in prognosis analysis and chemotherapy guidance for CCA patients?
MAD2 might be an excellent indicator in prognosis analysis and chemotherapy guidance for CCA patients.
AI Comments
👍 This article provides an insightful and comprehensive overview of the role of MAD2 in cholangiocarcinoma progression and the potential of using this marker for prognosis analysis and chemotherapy guidance.
👎 This article lacks sufficient detail on the experimental methods and results used to support its conclusions.
AI Discussion
Me: It discusses the role of MAD2 in the progression of cholangiocarcinoma. It explains how MAD2 activates the IGF1R/PI3K/AKT pathway and interferes with the USP44/LIMA1 complex to promote cholangiocarcinoma progression.
Friend: That's really interesting. What are the implications of this research?
Me: The research suggests that MAD2 can be used as an indicator in prognosis analysis and chemotherapy guidance for CCA patients. It also suggests that targeting MAD2 or the IGF1R/PI3K/AKT pathway may be a viable therapeutic approach for treating CCA.
Action items
- Research other studies related to MAD2 and cholangiocarcinoma progression.
- Investigate the potential of MAD2 as a prognostic indicator for CCA patients.
- Explore the therapeutic implications of MAD2 interference with USP44/LIMA1 complex in CCA treatment.
Technical terms
- MAD2
- Mitotic Arrest Deficient 2 like 1, a highly conserved member of the spindle assembly checkpoint (SAC) which plays an essential part in facilitating normal cell division.
- IGF1R/PI3K/AKT pathway
- A signaling pathway that is activated by the binding of insulin-like growth factor 1 (IGF1) to its receptor (IGF1R), which then activates the phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) pathways.
- USP44/LIMA1 complex
- A complex formed by ubiquitin specific peptidase 44 (USP44) and LIMA1 (LIM domain and actin-binding protein 1).
- PDTX
- Patient-derived tumor xenograft, a type of animal model used to study cancer.
- IHC
- Immunohistochemistry, a technique used to detect the presence of specific proteins in tissue samples.
- TMA
- Tissue microarray, a technique used to analyze multiple tissue samples simultaneously.