KEB and skin cancer

Understanding the growth and spread of skin cancer in KEB will help to identify potential future treatments.

Prof Valerie Brunton works in Edinburgh, UK, on a rare type of epidermolysis bullosa (EB) called Kindler EB. This is caused by genetic changes that mean the Kindlin-1 protein doesn’t work properly. Patients suffering with this form of EB have thin skin that blisters and sunburns easily and an increased risk of skin cancer (squamous cell carcinoma). This work studies how the growth and spread of skin cancer is related to Kindlin-1 protein.

Read more in our researcher's blog.

About our funding:

Research leader	Prof Valerie Brunton
Institution	University of Edinburgh, UK
Type of EB	KEB
Patient involvement	None
Funding amount	£230,271.67 (co-funded with DEBRA Austria)
Project length	3 years (extended due to Covid)
Start date	October 2020
DEBRA internal ID	Brunton2

Latest progress summary:

Cancer cells with the KEB genetic change (lack of kindlin-1) have been shown to be more likely to form secondary cancers in other parts of the body.
This work was presented in a talk to the Annual Meeting of the British Society for Investigative Dermatology in 2022 and in a poster at the 1st Edinburgh Skin Network Symposium in 2023.

About our researchers:

Research leader: Professor Valerie Brunton is Chair of Cancer Therapeutics at the University of Edinburgh. Her interests are in understanding the biology of Kindler EB associated with skin atrophy (weakening), photosensitivity, and an increased risk of developing cutaneous squamous cell cancer. Her research aims to identify the key molecular pathways that underlie the pathology of Kindler EB to help identify ways in which to treat this.

Co-researchers: Dr Adam Byron (biochemistry) University of Edinburgh and Prof Albena Dinkova-Kostova (cellular medicine) University of Dundee.

Collaborator: Dr Alan Serrels (cancer / tumour microenvironment) University of Edinburgh.

Why this research is important:

Our research has uncovered important changes in the tumour microenvironment (the normal cells and molecules that surround and support the growth of tumour cells), that are controlled by Kindlin-1. By studying these changes, we hope to gain a better understanding of how we can prevent the development and progression of skin cancer in patients with Kindler syndrome.

Prof Valerie Brunton

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Researcher's abstract:

Grant Title: Understanding the role of Kindlin-1 loss in the development of squamous cell carcinoma

Kindler EB (KEB) is a rare skin disorder that develops early in life. People with KEB have skin blistering and develop thin or papery skin. They are also highly sensitive to ultraviolet (UV) radiation from the sun and sunburn easily. KEB also increases the risk of developing a type of skin cancer called squamous cell carcinoma. KEB occurs due to a genetic mutation in the FERMT1 gene. Mutations in FERMT1 results in the production of a defective protein called Kindlin-1.
Currently there is very little known about why the loss of a functional Kindlin-1 protein in the skin of people with KEB increases their risk of developing squamous cell carcinoma (SCC). The group have previously carried out experiments on skin cells grown in the laboratory which has shown that loss of Kindlin-1 sensitises cells to UV radiation. To understand why this happens they will use a model which mimics sun exposure to UV radiation. The next stage will look at whether loss of Kindlin-1 in the skin leads to increased skin cancer formation following UV exposure.

The 3 aims of this project are:
Aim 1: Do changes in the tissue environment of tumours lacking Kindlin-1 contribute to their growth and metastatic spread?
Aim 2: Do Kindlin-1 binding partners (molecules that interact), regulate cancer (SCC) growth?
Aim 3: Does the loss of Kindlin-1 promote UV-induced skin cancer (SCC) formation?

DEBRA UK previously funded Professor Valerie Brunton at the University of Edinburgh towards research in Kindler Syndrome.

Researcher's progress update (2023):

Kindler EB (KEB) is a rare skin disorder that develops early in life. People with KEB have skin blistering, and develop thin or papery skin. They are also highly sensitive to ultraviolet (UV) radiation from the sun and sunburn easily. KEB also increases the risk of developing a type of skin cancer called squamous cell carcinoma. KEB occurs due to a genetic mutation in the FERMT1 gene. Mutations in FERMT1 result in the production of a defective protein called Kindlin-1. Currently there is very little known about why the loss of a functional Kindlin-1 protein in the skin of people with KEB increases their risk of developing squamous cell carcinoma. We have previously carried out experiments on skin cells grown in the laboratory which have shown that loss of Kindlin-1 sensitises cells to UV radiation. To understand why this happens we will use a model which mimics sun-exposure to UV radiation. This will identify UV-induced changes that are specifically controlled by loss of Kindlin. The next stage will look at whether loss of Kindlin-1 in the skin leads to increased skin cancer formation following UV exposure (From 2022 & 2023 progress reports.)