Highly malignant triple-negative breast cancer (TNBC) cells rely mostly on glycolysis to maintain cellular homeostasis; however, mitochondria are still required for migration and metastasis. Taking advantage of the metabolic flexibility of TNBC MDA-MB-231 cells to generate subpopulations with glycolytic or oxidative phenotypes, we screened phenolic compounds containing an ortho-carbonyl group with mitochondrial activity and identified a bromoalkyl-ester of hydroquinone named FR58P1a, as a mitochondrial metabolism-affecting compound that uncouples OXPHOS through a protonophoric mechanism. In contrast to well-known protonophore uncoupler FCCP, FR58P1a does not depolarize the plasma membrane and its effect on the mitochondrial membrane potential and bioenergetics is moderate suggesting a mild uncoupling of OXPHOS. FR58P1a activates AMPK in a Sirt1-dependent fashion. Although the activation of Sirt1/AMPK axis by FR58P1a has a cyto-protective role, selectively inhibits fibronectin-dependent adhesion and migration in TNBC cells but not in non-tumoral MCF10A cells by decreasing β1-integrin at the cell surface. Prolonged exposure to FR58P1a triggers a metabolic reprograming in TNBC cells characterized by down-regulation of OXPHOS-related genes that promote cell survival but comprise their ability to migrate. Taken together, our results show that TNBC cell migration is susceptible to mitochondrial alterations induced by small molecules as FR58P1a, which may have therapeutic implications.

Paper mulberry, Broussonetia papyrifera (L.) L’Hér. ex Vent. (Moraceae), a dioecious species, was transported by humans from Taiwan to the islands of Remote Oceania. Its introduction and cultivation in Remote Oceania was intentional due to its cultural importance as a fiber source for barkcloth textiles. The aim of this study was to explore the genetic diversity and structure of paper mulberry populations within Remote Oceania in order to infer dispersal patterns that may reflect past human interaction among island groups. We present the integrated analysis of 380 samples (313 contemporary and 67 herbarium specimens) collected in Near and Remote Oceania. Genetic characterization was based on a set of ten microsatellites developed for B . papyrifera and complemented with the analysis of the ribosomal internal transcribed spacer ITS-1 sequence, a sex marker and the chloroplast ndhF–rpl32 intergenic spacer. Microsatellite data identify a total of 64 genotypes, despite this being a clonally propagated crop, and show three major dispersal hubs within Remote Oceania, centered on the islands of Fiji, Tonga, and Pitcairn. Of 64 genotypes identified, 55 correspond to genotypes associated to female-sexed plants that probably descend from plants introduced by the prehistoric Austronesian-speaking voyagers. The ratio of accessions to genotypes between herbarium and contemporary samples, suggests recent loss of genetic diversity. In addition to the chloroplast haplotypes described previously, we detected two new haplotypes within Remote Oceania both originating in Taiwan. This is the first study of a commensal species to show genetic structuring within Remote Oceania. In spite of the genetic bottleneck, the presence of only one sex, a timespan of less than 5000 years, and asexual propagation of this crop in Remote Oceania, we detect genetic diversity and regional structuring. These observations suggest specific migration routes between island groups within Remote Oceania.

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Premise of the study:Broussonetia papyrifera (Moraceae) is native to Asia and is used as a medicinal plant and as a source of fiber for making paper. It was dispersed into the Pacific region as a fiber source for making nonwoven textiles (barkcloth). Microsatellites were developed to trace the human-mediated dispersal of this species into the Pacific region.Methods and Results:A set of 36 microsatellites was isolated and initially assayed on 10 accessions to assess polymorphism. We found that 20 markers were polymorphic, with the number of alleles per marker ranging from four to 35 in 70 accessions genotyped from three Asian populations. Observed and expected heterozygosities ranged from 0.04 to 0.85 and from 0.19 to 0.94, respectively. These markers were tested in four Moraceae species and one Rosaceae species.Conclusions:These markers will be useful for the assessment of genetic diversity in B. papyrifera. They show low transferability to other species tested.

Humans introduced paper mulberry (Broussonetia papyrifera) from Taiwan into the Pacific over 5000 years ago as a fiber source to make barkcloth textiles that were, and still are, important cultural artifacts throughout the Pacific. We have used B. papyrifera, a species closely associated to humans, as a proxy to understand the human settlement of the Pacific Islands. We report the first genetic analysis of paper mulberry textiles from historical and archaeological contexts (200 to 50 years before present) and compare our results with genetic data obtained from contemporary and herbarium paper mulberry samples. Following stringent ancient DNA protocols, we extracted DNA from 13 barkcloth textiles. We confirmed that the fiber source is paper mulberry in nine of the 13 textiles studied using the nuclear ITS-1 marker and by statistical estimates. We detected high genetic diversity in historical Pacific paper mulberry barkcloth with a set of ten microsatellites, showing new alleles and specific genetic patterns. These genetic signatures allow tracing connections to plants from the Asian homeland, Near and Remote Oceania, establishing links not observed previously (using the same genetic tools) in extant plants or herbaria samples. These results show that historic barkcloth textiles are cultural materials amenable to genetic analysis to reveal human history and that these artifacts may harbor evidence of greater genetic diversity in Pacific B. papyrifera in the past.