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  • Chronic Stress in Mice Remodels Lymph Vasculature to Promote Tumour Cell Dissemination

    Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although the pathways of tumour cell dissemination are unclear. Here we show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. We show that VEGFC derived from tumour cells is required for stress to induce lymphatic remodelling and that this depends on COX2 inflammatory signalling from macrophages. Pharmacological inhibition of SNS signalling blocks the effect of chronic stress on lymphatic remodelling in vivo and reduces lymphatic metastasis in preclinical cancer models and in patients with breast cancer.
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  • P53- and Mevalonate Pathway–Driven Malignancies Require Arf6 for Metastasis and Drug Resistance

    Application example of HvYolution Super-Resolution - Drug resistance, metastasis, and a mesenchymal transcriptional program are central features of aggressive breast tumors. The GTPase Arf6, often overexpressed in tumors, is critical to promote epithelial–mesenchymal transition and invasiveness. The metabolic mevalonate pathway (MVP) is associated with tumor invasiveness and known to prenylate proteins, but which prenylated proteins are critical for MVP-driven cancers is unknown. We show here that MVP requires the Arf6-dependent mesenchymal program.
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  • Mammary gland development

    Investigating the Influence of Hormone Signaling Pathways on Mammary Gland Development and the Onset of Breast Cancer

    Over their entire lifetime, 1 out of 8 women can suffer from breast cancer. The risk of developing breast cancer (mammary carcinogenesis) increases with a woman’s age and is related to her reproductive history. The chance of mammary carcinogenesis is less for women who give birth to a child before the age of 30. However, it is now known that the risk of breast cancer also can depend on the number of times a woman experiences elevated blood serum progesterone levels, in relation to the menstrual cycle, before her first pregnancy.
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