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Tspan8-β-catenin positive feedback loop promotes melanoma invasion.

Abstract：

:Due to its high proclivity to metastasize, and despite the recent development of targeted and immune therapy strategies, melanoma is still the deadliest form of skin cancer. Therefore, understanding the molecular mechanisms underlying melanoma invasion remains crucial. We previously characterized Tspan8 for its ability to prompt melanoma cell detachment from their microenvironment and trigger melanoma cell invasiveness, but the signaling events by which Tspan8 regulates the invasion process still remain unknown. Here, we demonstrated that β-catenin stabilization is a molecular signal subsequent to the onset of Tspan8 expression, and that, in turn, β-catenin triggers the direct transcriptional activation of Tspan8 expression, leading to melanoma invasion. Moreover, we showed that β-catenin activation systematically correlates with a high expression of Tspan8 protein in melanoma lesions from transgenic Nras; bcat* mice, as well as in deep penetrating naevi, a type of human pre-melanoma neoplasm characterized by a combined activation of β-catenin and MAP kinase signaling. Overall, our data suggest that β-catenin and Tspan8 are part of a positive feedback loop, which sustains a high Tspan8 expression level, conferring to melanoma cells the invasive properties required for tumor progression and dissemination.

journal_name

Oncogene

journal_title

Oncogene

authors

El Kharbili M,Agaësse G,Barbollat-Boutrand L,Pommier RM,de la Fouchardière A,Larue L,Caramel J,Puisieux A,Berthier-Vergnes O,Masse I

doi

10.1038/s41388-019-0691-z

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

3781-3793

issue

20

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-019-0691-z

journal_volume

38

pub_type

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