JAM3 (Junctional Adhesion Molecule 3)

P4, N=0, Completed, Shanghai Fengxian District Central Hospital; Shanghai Fengxian District Central Hospital

Pathways downstream of JAM3 were explored through RNA sequencing (RNA-seq) and Western Blot analysis, with rescue experiments using AKT inhibitor (MK2206) to validate pathway dependency...Conclusively, JAM3 acts as a tumor suppressor in SOC by modulating the PI3K/AKT pathway. These insights present JAM3 as a promising therapeutic target for SOC diagnosis and treatment.

The cut-off value for ∆Ct PAX1 was determined as 4.34 when maximizing the Youden index. PAX1 could be a promising triage marker in predicting the pathological upgrading of CIN before conization. We found that if the ∆Ct PAX1 cut-off value is lower than 4.34, it is highly suggestive of pathological upgrading.

DNA methylation testing outperformed LBC in triaging women with non-16/18 hrHPV infections, significantly reducing unnecessary colposcopy referrals, particularly when combined with HPV33/35 genotyping.

Further analysis, including Western blot and immunohistochemistry of xenograft tumor tissues, revealed that increased JAM3, stimulated by USF1, activates the Hippo signaling pathway, underscoring its role in tumor suppression. These findings position USF1 and JAM3 as pivotal elements in the molecular framework of LSCC, suggesting their potential as targets for therapeutic intervention.

The PAX1/JAM3 methylation detection exhibited excellent accuracy in identifying cervical precancerous lesions in HPV 16/18-positive women and could be considered as a triage tool to reduce excessive referrals for colposcopy and overtreatment.

Knockdowning and blocking JAM3 sensitized cancer cells to ferroptosis inducers RSL3 and erastin, while JAM3 overexpression conferred resistance to these agents. In addition, JAM3 also promoted ovarian cancer cells resistance to chemotherapeutic agent cisplatin in vitro and in vivo by inhibiting ferroptosis...Moreover, JAM3 high expression was associated with poor prognosis in patients with ovarian cancer. Altogether, this study provided novel insights into the molecular mechanisms underlying ferroptosis resistance and identify JAM3 as a potential therapeutic target for combating drug resistance in ovarian cancer.

JAM3 can serve as a key negative regulator of breast cancer cell invasion, apoptosis, and brain metastasis, possibly through the TGF/Smad signaling pathway. JAM3 is anticipated to be a promising biomarker for the diagnosis and prognosis of breast cancer.

P=N/A, N=50, Recruiting, First Hospital of Shanxi Medical University; First Hospital of Shanxi Medical University

In conclusion, our results suggested that JAM3 promotes cervical cancer cell migration and invasion by activating the HIF-1α/VEGFA pathway. JAM3 may be a promising biomarker and effective therapeutic target for cervical cancer.

The JAM3/PAX1 gene methylation test can be used independently for the stratified diagnosis of high-grade/non-high-grade cervical lesions in women with high-risk human papillomavirus infection, independent of the cytological results of cervical excision. The JAM3/PAX1 gene methylation test can also be used in combination with LBC to make up for the shortcomings of low sensitivity of LBC. In addition, the application of methylation kit in large-scale cervical cancer screening in the future will be good to the detection of more patients with high-grade cervical lesions, and achieve early screening and early treatment for cervical lesions/cancer.

The immune checkpoint CD200 also showed a positive correlation with JAM3. Our findings revealed that elevated JAM3 levels are predictive of poor prognosis and immune cell infiltration in BC patients by regulating EMT process.