IGFBP5 (Insulin Like Growth Factor Binding Protein 5)

This FOSB-mediated upregulation of IGFBP5 expression subsequently weakened the susceptibility of IGF1R to IGF-1 stimulation and suppressed the downstream PI3K/Akt and Ras/Raf/ERK oncogenic pathways. Our findings identify the novel FOSB-IGFBP5-IGF-1 axis upstream of PI3K/Akt and Ras/Raf/ERK signalling as a key regulator of PCa progression.

After failure of gemcitabine/docetaxel chemotherapy, next-generation sequencing identified an IGFBP5-ALK fusion (breakpoint: IGFBP5 exon 1 - ALK exon 19), a TERT promoter mutation, and a homozygous CDKN2A/CDKN2B/MTAP deletion. This case highlights the first documented response to an ALK inhibitor in ALK-rearranged HG-ESS. The findings underscore the importance of comprehensive molecular profiling in identifying targetable alterations in rare sarcomas and support the use of iruplinalkib as an effective therapeutic option in this setting.

This proof-of-concept study demonstrates that a machine learning-assisted multiplex autoantibody assay offers a feasible noninvasive approach for CMT detection. Further validation in larger, independent cohorts is warranted to support clinical translation in veterinary oncology.

Moreover, combined treatment with the RSK2 inhibitor LJH685 and the IGF1R inhibitor PPP significantly reduces metastasis of triple-negative breast cancer (TNBC) in both in vitro and in vivo models. These findings uncover new targets for synergistic antitumor therapy in TNBC and suggest that concurrent inhibition of IGF1R and RSK2 may offer an effective combinatorial treatment strategy.

ROC analyses revealed that IGF-1, IGFBP-4, and IGFBP-5 have good discriminatory properties in the diagnosis of gastric cancer, while PAPP-A offers low diagnostic value. In conclusion, this study suggests that IGF pathway components, particularly IGF-1, IGFBP-4, and IGFBP-5, might be promising biomarker candidates for gastric cancer.

Immunohistochemistry suggested that in osteosarcoma patients with poorer prognosis, the expression of these four hub genes was significantly elevated. We have developed an effective model for predicting osteosarcoma prognosis and immune response, which may provide valuable insights for osteosarcoma prognostic evaluation and immune therapy strategies.

Furthermore, IGFBP5, KRT14 and SERPINF1 were found to be linked to poor survival outcomes in BC, with their expression levels notably elevated in BC cell lines compared to a normal bladder cell line. This study identified potential prognostic marker genes for BC, offering valuable insights into the prediction of patient survival outcomes.

Multiplex immunofluorescence in primary PCa confirmed increased PD-L1 in patients with high serum IGF-1, supporting its role in immune evasion. Overall, these findings reveal a novel IGF-1-driven immunosuppressive mechanism that may underlie PCa's resistance to immunotherapy.

Additionally, expression of genes involved in adipocyte differentiation and remodeling (perilipin 1, perilipin 2, Pparγ, fatty acid synthase, and metalloproteinase 3) was unaltered. In conclusion, under the conditions and doses evaluated, BP3 exposure during pregnancy or during mammary epithelial cell differentiation does not alter mammary involution.

Targeting CREB using a pharmacological inhibitor reversed the IGFBP5 induced phenotypes. These findings further support the role of preadipocytes in ovarian cancer progression and suggest therapeutically targeting IGFBP5 or CREB may reduce ovarian cancer metastasis.

We further revealed conserved regulatory mechanisms conserved across species, as intratumor HIF-1α enhances the production of IGFBP-5, a mammalian homolog of fly ImpL2, contributing to organ wasting in both tumor-bearing mice and patients. Therefore, our study provides novel insights into the mechanisms by which tumors regulate production of cachectic ligands and the pathogenesis of cancer-induced cachexia.

Moreover, rescue experiments reveal that IGFBP5 overexpression can attenuate the progression induced by miR-103a-3p in gastric cancer cells. In summary, our findings suggest that the miR-103a-3p/IGFBP5 axis may play a role in gastric cancer progression, highlighting its potential as a therapeutic target and prognostic marker.