Biology subjects

Rodrigues, A. A.

Publications and source records attributed to Rodrigues, A. A..

2 recordsLinked to original sources

bioRxiv2025

Midkine inhibits dormancy of disseminated melanoma cells

A major challenge in melanoma treatment is the emergence of aggressive metastases from previously dormant disseminated cancer cells (DCCs). Here we identify Midkine (MDK) as a key factor that disrupts melanoma DCC dormancy by triggering an autocrine signal that suppresses the dormancy inducer NR2F1 and alters the p-p38/p-ERK ratio, via ALK signaling. Dormant melanoma DCCs in lymph nodes and visceral tissues exhibit an MDKLOW/NR2F1HIGH phenotype. Transient NR2F1 activation for one month with a potent agonist counteracts MDK-driven mTORC1 activity and suppresses lung metastasis in mice bearing human melanoma DCCs. Dual targeting of MDK (genetic blockade) and NR2F1 (activation) markedly limits metastatic outgrowth and extends survival for 6 months in mouse models independent of BRAF status. These findings support the MDK-NR2F1 axis as a promising therapeutic target to sustain dormancy and prevent melanoma recurrence. Statement of SignificanceThis work identifies Midkine as a key disruptor of tumor dormancy in melanoma, driving metastatic awakening via NR2F1 suppression. Dual targeting of Midkine (inhibition) and NR2F1 (activation) prolongs survival in preclinical models.

cancer biology↗

bioRxiv2024

Defensive symbiont genotype distributions are linked to parasitoid attack networks

Facultative symbionts are widespread in arthropods and can provide important services such as protection from natural enemies. Yet what shapes associations with defensive symbionts in nature remains unclear. Two hypotheses suggest that either interactions with antagonists, or host plants, may explain the prevalence of symbionts through shared selective pressures and routes of horizontal transmission. Here we investigate the factors driving similarities in the Hamiltonella defensa symbiosis shared among host species within field collected aphid communities. We show that, Hamiltonellas genotype distribution strongly aligns with sharing the same parasitoids, rather than host plants, highlighting parasitoids as a key selective agent shaping the symbiosis across host species. Our data indicates parasitoid host-specificity drives the prevalence of specific aphid-Hamiltonella associations, suggesting defensive symbioses are maintained by the selective pressure imposed by dominant parasitoid species. These findings underscore the importance of interactions with natural enemies in explaining patterns of defensive symbiosis in nature.

ecology↗