Qiqiao Du

Cuproptosis inhibits tumor progression and enhances cisplatin toxicity in ovarian cancer

Abstract Cuproptosis is a novel form of regulated cell death triggered by copper ion and copper ionophore. While cuproptosis has been actively explored as a potential target for cancer therapy, its role in ovarian cancer (OC) still remains unclear. In this study, we demonstrate that cuproptosis inhibits OC cell proliferation, migration, and invasion through FDX1 regulation and suppresses tumor growth in a mouse model. We also confirm that cuproptosis enhances OC sensitivity to cisplatin treatment both in vivo and in vitro. Moreover, our findings reveal that cuproptosis affects cholesterol biosynthesis in OC cells, with cholesterol playing a crucial role in its cytotoxic effect. Taken together, our results elucidate the effect of cuproptosis in OC and suggest it as a promising therapeutic strategy.

Targeting CDCP1 boost CD8+ T cells-mediated cytotoxicity in cervical cancer via the JAK/STAT signaling pathway

Background Cervical cancer remains a global health challenge. The identification of new immunotherapeutic targets may provide a promising platform for advancing cervical cancer treatment. Objective This study aims to investigate the role of CUB domain-containing protein 1 (CDCP1) in cervical cancer progression and evaluate its potential as a therapeutic target. Methods We performed comprehensive analyses using patient cohorts and preclinical models to examine the association between CDCP1 expression and cervical cancer prognosis. Then in immunodeficient and immunocompetent mouse models, we further investigated the impact of CDCP1 on the tumor immune microenvironment, focusing on its effects on tumor-infiltrating T cells, including cytotoxic T lymphocytes (CTLs) and regulatory T cells (Tregs). Mechanistic studies were performed to elucidate the pathways involved in CDCP1-mediated immune modulation, in particular its interaction with the T cell receptor CD6 and the activation of the JAK-STAT signaling pathway. Results Our results show that CDCP1 overexpression is associated with poor prognosis and T cell infliction in cervical cancer. Specifically, it affects the activity of CTLs and Tregs. Mechanistically, CDCP1 binds to CD6 and inhibits the JAK-STAT pathway of T cells. The study further demonstrates that targeting CDCP1 with the inhibitor 8-prenylnaringenin (8PN) effectively suppresses tumor growth in vivo and enhances antitumor immunity. Conclusions CDCP1 plays a critical role in cervical cancer progression by modulating the tumor immune microenvironment. Targeting CDCP1 offers a promising therapeutic strategy to improve the outcome of patients with cervical cancer.

FASN promotes lymph node metastasis in cervical cancer via cholesterol reprogramming and lymphangiogenesis

AbstractCervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. Clarification of the detailed mechanisms underlying LNM may provide potential clinical therapeutic targets for CC patients with LNM. However, the molecular mechanism of LNM in CC is unclear. In the present study, we demonstrated that fatty acid synthase (FASN), one of the key enzymes in lipid metabolism, had upregulated expression in the CC samples and was correlated with LNM. Moreover, multivariate Cox proportional hazards analysis identified FASN as an independent prognostic factor of CC patients. Furthermore, gain-of-function and loss-of-function approaches showed that FASN promoted CC cell migration, invasion, and lymphangiogenesis. Mechanistically, on the one hand, FASN could regulate cholesterol reprogramming and then activate the lipid raft-related c-Src/AKT/FAK signaling pathway, leading to enhanced cell migration and invasion. On the other hand, FASN induced lymphangiogenesis by secreting PDGF-AA/IGFBP3. More importantly, knockdown of FASN with FASN shRNA or the inhibitors C75 and Cerulenin dramatically diminished LNM in vivo, suggesting that FASN plays an essential role in LNM of CC and the clinical application potential of FASN inhibitors. Taken together, our findings uncover a novel molecular mechanism in LNM of CC and identify FASN as a novel prognostic factor and potential therapeutic target for LNM in CC.