FOXC2 (Forkhead Box C2)

Disruption of LAMA4-ITGA6 binding substantially attenuated FOXC2-LAMA4-mediated metastatic burden. These results reveal a novel mechanism by which FOXC2+ tumor cells promote metastasis in advanced ccRCC and further establish the therapeutic potential of targeting FOXC2-LAMA4 in blocking the metastatic cascade of ccRCC.

Our findings collectively elucidate the regulatory role, functional significance, and underlying mechanism of cyclic RNA0002898 in HCC, a previously uncharted relationship. The potential prognostic implications of cyclic RNA0002898 and its therapeutic potential as a target in HCC warrant further investigation.

Breast cancer cells proliferated in the core of all prototypes designed, forming spheroids and cell aggregates with a high resistance to doxorubicin. The addition of Collagen I to the developed model enabled the upregulation of malignancy markers (Col1A1, Ki67, FOXC2, SNAI1, NFKB1, WWTR1), invasion markers (WASL, ACTA1, MYO1E, TPM4, PODXL, ITGA2, ITGA5, MENA, EGFR, CDC42), and drug resistance markers (ABCG2, CYP1A1, BAX, HSP90AA1) occurring in vivo. The developed 3D in vitro model can clarify the contribution of the extracellular matrix to the tumor outcome and drug efficacy by replicating some key characteristics of breast tumors, establishing a novel tool for chemotherapeutic agents and drug screening.

Prox1 played an important role in promoting cell proliferation, migration, and lymphangiogenesis, which is related to tumor metastasis and poor prognosis. These results indicated the potential importance of Prox1 as a biomarker, which is expected to lead to the development of a new insight for anti-tumor therapy.

We also show pHi dynamics can override mechanosensitive cell responses to the extracellular microenvironment. Thus, our work positions pHi as an integrator of mechanotransduction in cancer, suggesting a new framework for therapeutically targeting pHi in cancer and perhaps in other diseases driven by ECM remodeling.

The ERK inhibitor GDC-0994 exhibited significant synergistic effects with the AR inhibitor bicalutamide. Specifically, the combination therapy inhibits FOXC2-driven EMT and induces ferroptosis via the FOXC2-Hippo signaling axis, suppressing tumor proliferation, migration, and invasion. In summary, this study uncovers the value of AR/ERK co-targeting in TNBC, which might potentiate the development of novel targeted therapeutic strategies in TNBC.

These results suggest that SNAIL and FOXC2 could serve as potential prognostic biomarkers in MBCSCs, whereas HOTAIR, UCA1, MALAT1, and ZEB may not independently predict metastasis or survival outcomes. Further research is necessary to explore the therapeutic implications of these genes in metastatic breast cancer.

These findings unravelled a mechanism whereby the hybrid EMT state regulates stemness, self-renewal and differentiation via transient Wnt/ERK/CDK4/6 activation, which can be leveraged for cancer-stem cell therapy.

Furthermore, six potential therapeutic agents for EC were identified: BIRB.0796, Camptothecin, CHIR.99021, Methotrexate, PF.4708671, and Vorinostat. Furthermore, several potential therapeutic agents for EC were identified, offering promising avenues for treatment. These findings hold significant potential for enhancing the survival outcomes of EC patients and provide meaningful guidance for clinical decision-making in managing this malignancy.

Late FDIM exhibited immune microenvironment remodelling, immune evasion, and apoptosis inhibition (e.g., BIRC2, BIRC5, CCL2, HAVCR2), with downregulation of FOX1, FOXC2, and SOX11. These results provide critical biomarkers of disease severity, which may aid in the development of more accurate prognostic tests and more effective targeted therapies for FDIM.

Furthermore, the protein levels of HOXA1, fibronectin, and FOXC2 were downregulated, while GRHL2 and E-cadherin expressions were increased in the si-RNF217-AS1 group (P<0.01). RNF217-AS1 is upregulated in esophageal cancer cells, and its downregulation inhibits the proliferation, migration and EMT of esophageal cancer cells by regulating the miR-377-3p/HOXA1 axis.

This study establishes USP6NL as a key modulator of CRC progression, regulating proliferation, apoptosis, migration, angiogenesis, and metabolic pathways. The loss of USP6NL leads to EMT suppression, apoptosis induction, and reduced tumor cell viability, positioning it as a potential therapeutic target in colorectal cancer. Further investigations are warranted to explore USP6NL's interactions in oncogenic signaling networks and its feasibility as a target for CRC therapy. It could serve as a promising therapeutic target in colorectal cancer, potentially enhancing tumor cell death and limiting metastasis. Targeting USP6NL could also provide a novel approach in combination with existing therapies, improving treatment efficacy and reducing side effects.