Coupled fibromodulin and SOX2 signaling as a critical regulator of metastatic outgrowth in melanoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-06-23

AUTHORS

Victor O. Oria, Hongyi Zhang, Christopher R. Zito, Chetan K. Rane, Xian-Yong Ma, Olivia K. Provance, Thuy T. Tran, Adebowale Adeniran, Yuval Kluger, Mario Sznol, Marcus W. Bosenberg, Harriet M. Kluger, Lucia B. Jilaveanu

ABSTRACT

We aimed to study mechanisms controlling metastatic outgrowth of melanoma into clinically relevant lesions, a critical process responsible for the majority of melanoma deaths. To this end, we developed novel in vivo models and identified molecular events that can be ascribed to their distinct phenotypes, indolent or highly metastatic. Induction of a proliferative state at distant sites was associated with high levels of the stem-like/progenitor marker, SOX2, and required the upregulation of FMOD, an extracellular matrix component, which modulates tumor–stroma interactions. Functional studies revealed a possible link between FMOD and SOX2; dual FMOD and SOX2 silencing nearly abolished brain metastasis and had a similar effect on distant metastasis to other sites. Our in vitro data suggests that FMOD and SOX2 cooperation plays an important role in tumor vasculogenic mimicry. Furthermore, we found that FMOD and SOX2 functional roles might converge at the activation of transcriptional co-factors YAP and TAZ, possibly via crosstalk with the tumor suppressor Hippo pathway. Finally, high expression of both genes in patient specimens predicted early development of brain metastasis. Thus, our study identifies FMOD and SOX2 cooperation as a novel regulatory mechanism that might be linked functionally to melanoma metastatic competence. More... »

PAGES

377

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00018-022-04364-5

    DOI

    http://dx.doi.org/10.1007/s00018-022-04364-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1148906456

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35737114


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