Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return resulting in swelling of the extremities and accumulation of undrained interstitial fluid/lymph that results in fibrosis and adipose tissue deposition in the limb. Whereas it is clearly established that primary lymphedema is sex-linked with an average ratio of one male for three females, the role of female hormones, in particular estrogens, has been poorly explored. In addition, secondary lymphedema in Western countries affects mainly women who developed the pathology after breast cancer and undergo through hormone therapy up to five years after cancer surgery. Although lymphadenectomy is identified as a trigger factor, the effect of co-morbidities associated to lymphedema remains elusive, in particular, estrogen receptor antagonists or aromatase inhibitors. In addition, the role of sex hormones and gender has been poorly investigated in the etiology of the pathology. Therefore, this review aims to recapitulate the effect of sex hormones on the physiology of the lymphatic system and to investigate whetherhormone therapy could promote a lymphatic dysfunction leading to lymphedema.

Stau1 is a pluripotent RNA-binding protein that is responsible for the post-transcriptional regulation of a multitude of transcripts. Here, we observed that lung cancer patients with a high Stau1 expression have a longer recurrence free survival. Strikingly, Stau1 did not impair cell proliferation in vitro, but rather cell migration and cell adhesion. In vivo, Stau1 depletion favored tumor progression and metastases development. In addition, Stau1 depletion strongly impaired vessel maturation. Among a panel of candidate genes, we specifically identified the mRNA encoding the cell adhesion molecule Thrombospondin 1 (THBS1) as a new target for Staufen-mediated mRNA decay. Altogether, our results suggest that regulation of THBS1 expression by Stau1 may be a key process involved in lung cancer progression.