TRIB3 overexpression

TRIB3 overexpression is significantly linked to malignant progression and unfavorable prognosis in diverse solid tumors. These results suggest that TRIB3 holds promise as a biomarker and therapeutic target in human cancers.

Functionally, a combined treatment of palbociclib with ferroptosis inducer significantly suppressed prostate cancer growth in a xenograft tumor model. Together, these results uncover an essential role of TRIB3/SOX2/SLC7A11 axis in palbociclib-induced ferroptosis, suggesting palbociclib a promising targeted therapy in combine with ferroptosis induction for the treatment of prostate cancer.

This simultaneously helps facilitate the accumulation of lipids while preserving ER homeostasis, thus driving accelerated RCC tumor progression. This TRIB3-PLIN2 axis thus represents a promising new target for efforts to treat RCC.

Our study provides insights into cancer angiogenesis and offers a potential therapeutic strategy for TRIB3-overexpressed cancer.

Single-cell sequencing showed that localization and binding targets of TRIB3 mainly involved monocytes/macrophages and CD4 and CD8 T cells. Overall, our study revealed that elevated TRIB3 expression represents a promising prognostic marker for ccRCC patients and may play a key role in tumor microenvironment modulation.

Indeed, co-immunoprecipitation assays demonstrated that TRIB3 interacts with SMARCD3 in the nucleus, suggesting that it may regulate TRIB3 in HCCs. This study demonstrated that TRIB3 promotes the malignancy of HCC cells and its expression may be a potential diagnostic biomarker for HCC progression.

Disruption of TRIB3 increases C/EBP-ATF-driven transcription, augments ER stress and cell death upon exposure to bortezomib, while TRIB3 overexpression enhances cell survival. Thus, TRIB3, colocalizing with ATF4 and limiting its transcriptional activity, functions as a factor increasing resistance to bortezomib, while pharmacological over-activation of eIF2α-ATF4 can overcome the endogenous restraint mechanisms and sensitize cells to bortezomib.

This study demonstrated that TRIB3 acts as an oncogene and plays a crucial role in the proliferation and invasion of RB cells via regulating the AKT/mTOR signaling pathway. Therefore, TRIB3 may serve as a potential target in the diagnosis and/or treatment of RB.

Moreover, the results suggested that TRIB3 overexpression increased the phosphorylation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR), whereas TRIB3 knockdown decreased the phosphorylation of AKT and mTOR compared with control cells. To summarize, the present study indicated that TRIB3 promoted OSCC cell proliferation by activating the AKT signaling pathway; therefore, TRIB3 may serve as a potential target for the diagnosis and treatment of OSCC.

Furthermore, our data indicated that TRIB3 knockdown decreased hypoxia-inducible factor (HIF)1α levels and targeted the glycolytic genes regulated by HIF1α. Together, our findings revealed a previously unappreciated function of TRIB3 in cancer cell metabolism and tumor progression, illustrating that TRIB3 could be considered a valuable therapeutic target for LUAD patients.