The Neurodevelopmental Protein POGZ Suppresses Metastasis in Triple-Negative Breast Cancer by Attenuating TGFβ Signaling.

Autor:	Heath J; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.; Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada., Mirabelli C; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.; Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada., Annis MG; Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada., Sabourin V; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada., Hebert S; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada., Findlay S; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada., Kim H; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada., Witcher M; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada., Kleinman CL; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.; Department of Human Genetics, McGill University, Montreal, Quebec, Canada., Siegel PM; Goodman Cancer Institute, McGill University, Montreal, Quebec, Canada.; Department of Medicine, McGill University, Montreal, Quebec, Canada.; Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia., Orthwein A; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.; Department of Biochemistry, McGill University, Montreal, Quebec, Canada., Ursini-Siegel J; Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.; Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.; Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2024 Nov 15; Vol. 84 (22), pp. 3743-3760.
DOI:	10.1158/0008-5472.CAN-23-3887
Abstrakt:	The pogo transposable element-derived zinc finger protein, POGZ, is notably associated with neurodevelopmental disorders through its role in gene transcription. Many proteins involved in neurological development are often dysregulated in cancer, suggesting a potential role for POGZ in tumor biology. Here, we provided experimental evidence that POGZ influences the growth and metastatic spread of triple-negative breast cancers (TNBC). In well-characterized models of TNBC, POGZ exerted a dual role, both as a tumor promoter and metastasis suppressor. Mechanistically, loss of POGZ potentiated TGFβ pathway activation to exert cytostatic effects while simultaneously increasing the mesenchymal and migratory properties of breast tumors. Although POGZ levels are elevated in human breast cancers, the most aggressive forms of TNBC tumors, including those with increased mesenchymal and metastatic properties, exhibit dampened POGZ levels, and low POGZ expression was associated with inferior clinical outcomes in these tumor types. Taken together, these data suggest that POGZ is a critical suppressor of the early stages of the metastatic cascade. Significance: The POGZ neurodevelopmental protein plays dual functions in triple-negative breast cancers as a tumor promoter and metastasis suppressor, inhibiting TGFβ-regulated EMT to limit breast cancer metastatic progression. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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