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- Aleckovic, M, et al.
(författare)
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Breast cancer prevention by short-term inhibition of TGFβ signaling
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 7558-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer prevention has a profound impact on cancer-associated mortality and morbidity. We previously identified TGFβ signaling as a candidate regulator of mammary epithelial cells associated with breast cancer risk. Here, we show that short-term TGFBR inhibitor (TGFBRi) treatment of peripubertal ACI inbred and Sprague Dawley outbred rats induces lasting changes and prevents estrogen- and carcinogen-induced mammary tumors, respectively. We identify TGFBRi-responsive cell populations by single cell RNA-sequencing, including a unique epithelial subpopulation designated secretory basal cells (SBCs) with progenitor features. We detect SBCs in normal human breast tissues and find them to be associated with breast cancer risk. Interactome analysis identifies SBCs as the most interactive cell population and the main source of insulin-IGF signaling. Accordingly, inhibition of TGFBR and IGF1R decrease proliferation of organoid cultures. Our results reveal a critical role for TGFβ in regulating mammary epithelial cells relevant to breast cancer and serve as a proof-of-principle cancer prevention strategy.
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| 2. |
- Garmroudi, F., et al.
(författare)
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Unveiling the structure-property relationship in metastable Heusler compounds by systematic disorder tuning
- 2023
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Ingår i: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 107:1
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Tidskriftsartikel (refereegranskat)abstract
- Heusler compounds represent a unique class of materials that exhibit a wide range of fascinating and tuneable properties such as exotic magnetic phases, superconductivity, band topology, or thermoelectricity. An exceptional, but for Heusler compounds common, feature is that they are prone to antisite defects and disorder. In this regard, the Fe2VAl Heusler compound has been a particularly interesting and disputed candidate. Even though various theoretical scenarios for the interplay of physical properties and disorder have been proposed, the metastable disordered A2 phase hitherto precluded experimental investigation in bulk samples. Here, we report experimental results on disorder-tuned Fe2VAl0.9Si0.1 alloys all the way toward the A2 phase, which we realized via rapidly quenching our samples from high temperatures. We measured the thermoelectric properties of these materials in a wide temperature range (4 to 700 K); they suggest a gradual semimetal/narrow-gap semiconductor -> metal transition upon increasing the disorder. We also find a large anomalous Hall effect in the disordered A2 phase, arising from the side-jump scattering of charge carriers at the antisite magnetic moments. This is corroborated by measurements of the temperature-and field-dependent magnetization, which increases dramatically up to approximate to 2.5 mu B/f.u. as compared to the ordered compound (<0.1 mu B/f.u.). This study provides an experimental realization of the metastable A2 structure in bulk Fe2VAl-based alloys and grants insight into the structure-property relationship of these materials. Our work confirms that temperature-induced antisite disorder, occurring during thermal heat treatment, can be a precisely tuneable parameter in the family of Heusler compounds.
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