Understanding the adhesome network in primary and metastatic cutaneous squamous cell carcinoma
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Date
06/07/2019Author
Li Mow Chee, Frederic Paul Li Kwet Khiong
Metadata
Abstract
Understanding how cancer cells survive, invade and migrate is of
fundamental importance to the development of approaches to
inhibit invasion and metastasis in patients. Proteins recruited at
adhesion complexes, known as the adhesome, are involved in
multiple mechanisms which control cancer cell behaviour. Here,
we used a proteomic and network analysis approach to perform a
global assessment of functional molecular units associated with
cancer cell progression in the context of the adhesome. We
present the functional modules of the adhesome at different
stages of human cutaneous squamous cell carcinoma (SCC)
progression. From the network analysis, we found that exportin-1,
a mediator of protein export from the nucleus to the cytoplasm, is
an important hub during cancer progression. Interestingly, one of
the interactors of exportin-1 is the actin-regulator Mena. We
found that Mena has a nuclear function in metastatic SCC cells
and that the nucleocytoplasmic shuttling of Mena is regulated by
integrin activation and focal adhesion kinase (FAK). Moreover,
our preliminary results suggest that Mena may act as a molecular
clutch for the mechanosensing function of Nesprin-2 with actin.
The putative molecular clutch activity of Mena regulates the
phosphorylation of EMERIN and possibly affects histone
methylation. Here, we propose a novel mechanism by which
Mena may regulate metastasis during SCC progression.