Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Loss of Golga7 Suppresses Oncogenic Nras‐Driven Leukemogenesis without Detectable Toxicity in Adult Mice
https://orcid.org/0000-0002-9783-0064
AbstractNRAS mutations are prevalent in human hematological malignancies and are also common in certain solid tumors, including melanoma and colon cancer. Despite their crucial role in oncogenesis, no effective therapies targeting NRAS have been developed. Inhibiting NRAS localization to the plasma membrane (PM) represents a promising strategy for cancer therapy, as its oncogenic signaling relies on PM localization. Knocking out Golgin subfamily A member 7 (Golga7), an accessory protein of RAS palmitoyltransferases, through a conditional gene editing approach drastically suppresses the development of myeloid leukemia induced by the activation of NrasG12D/G12D knock‐in alleles in mice. The loss of Golga7 disrupts NRASG12D PM localization in bone marrow cells without altering the level of NRASG12D palmitoylation. Notably, Golga7 is dispensable for normal hematopoiesis in adult mice. While constitutive Golga7 knockout leads to embryonic lethality, the ubiquitous knockout of Golga7 induced in adult mice does not manifest any measurable toxic effects. These findings indicate that GOLGA7 is an effective and safe therapeutic target for NRAS‐driven leukemias.
Loss of Golga7 Suppresses Oncogenic Nras‐Driven Leukemogenesis without Detectable Toxicity in Adult Mice
https://orcid.org/0000-0002-9783-0064
AbstractNRAS mutations are prevalent in human hematological malignancies and are also common in certain solid tumors, including melanoma and colon cancer. Despite their crucial role in oncogenesis, no effective therapies targeting NRAS have been developed. Inhibiting NRAS localization to the plasma membrane (PM) represents a promising strategy for cancer therapy, as its oncogenic signaling relies on PM localization. Knocking out Golgin subfamily A member 7 (Golga7), an accessory protein of RAS palmitoyltransferases, through a conditional gene editing approach drastically suppresses the development of myeloid leukemia induced by the activation of NrasG12D/G12D knock‐in alleles in mice. The loss of Golga7 disrupts NRASG12D PM localization in bone marrow cells without altering the level of NRASG12D palmitoylation. Notably, Golga7 is dispensable for normal hematopoiesis in adult mice. While constitutive Golga7 knockout leads to embryonic lethality, the ubiquitous knockout of Golga7 induced in adult mice does not manifest any measurable toxic effects. These findings indicate that GOLGA7 is an effective and safe therapeutic target for NRAS‐driven leukemias.
Loss of Golga7 Suppresses Oncogenic Nras‐Driven Leukemogenesis without Detectable Toxicity in Adult Mice
https://orcid.org/0000-0002-9783-0064
AbstractNRAS mutations are prevalent in human hematological malignancies and are also common in certain solid tumors, including melanoma and colon cancer. Despite their crucial role in oncogenesis, no effective therapies targeting NRAS have been developed. Inhibiting NRAS localization to the plasma membrane (PM) represents a promising strategy for cancer therapy, as its oncogenic signaling relies on PM localization. Knocking out Golgin subfamily A member 7 (Golga7), an accessory protein of RAS palmitoyltransferases, through a conditional gene editing approach drastically suppresses the development of myeloid leukemia induced by the activation of NrasG12D/G12D knock‐in alleles in mice. The loss of Golga7 disrupts NRASG12D PM localization in bone marrow cells without altering the level of NRASG12D palmitoylation. Notably, Golga7 is dispensable for normal hematopoiesis in adult mice. While constitutive Golga7 knockout leads to embryonic lethality, the ubiquitous knockout of Golga7 induced in adult mice does not manifest any measurable toxic effects. These findings indicate that GOLGA7 is an effective and safe therapeutic target for NRAS‐driven leukemias.
Loss of Golga7 Suppresses Oncogenic Nras‐Driven Leukemogenesis without Detectable Toxicity in Adult Mice
Advanced Science
Jiao, Bo (Autor:in) / Yan, Lei (Autor:in) / Zhang, Rui (Autor:in) / Huang, Wei (Autor:in) / Wang, Xinru (Autor:in) / Liu, Chenxuan (Autor:in) / Wang, Peihong (Autor:in) / Xu, Pengfei (Autor:in) / Wang, Jinzeng (Autor:in) / Fang, Zhou (Autor:in)
17.03.2025
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
| British Library Online Contents | 1999
| Wiley | 2021