TGFβ-induced expression of long noncoding lincRNA Platr18 controls breast cancer axonogenesis.

Autor:	Grelet S; Department of Biochemistry and Molecular Biology, College of Medicine, University of South Alabama, Mobile, AL, USA sgrelet@southalabama.edu.; Mitchell Cancer Institute, The University of South Alabama, Mobile, AL, USA.; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA.; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA., Fréreux C; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA., Obellianne C; Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, USA., Noguchi K; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.; Center for Family Medicine, Sioux Falls, SD, USA., Howley BV; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA., Dalton AC; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA., Howe PH; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA howep@musc.edu.; Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2021 Nov 22; Vol. 5 (2). Date of Electronic Publication: 2021 Nov 22 (Print Publication: 2022).
DOI:	10.26508/lsa.202101261
Abstrakt:	Metastasis is the leading driver of cancer-related death. Tumor cell plasticity associated with the epithelial-mesenchymal transition (EMT), an embryonic program also observed in carcinomas, has been proposed to explain the colonization of distant organs by the primary tumor cells. Many studies have established correlations between EMT marker expression in the primary tumor and metastasis in vivo. However, the longstanding model of EMT-transitioned cells disseminating to secondary sites is still actively debated and hybrid states are presently considered as more relevant during tumor progression and metastasis. Here, we describe an unexplored role of EMT on the tumor microenvironment by controlling tumor innervation. Using in vitro and in vivo breast tumor progression models, we demonstrate that TGFβ-mediated tumor cell EMT triggers the expression of the embryonic LincRNA Platr18 those elevated expression controls the expression of the axon guidance protein semaphorin-4F and other neuron-related molecules such as IGSF11/VSIG-3. Platr18/Sema4F axis silencing abrogates axonogenesis and attenuates metastasis. Our observations suggest that EMT-transitioned cells are also locally required in the primary tumor to support distant dissemination by promoting axonogenesis, a biological process known for its role in metastatic progression of breast cancer. (© 2021 Grelet et al.)
Databáze:	MEDLINE
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