Under your skin: taking skin cancer out by its roots

Tumours can spring up amongst
'fields' of healthy skin cells.

The summer sun may finally be on its way. This is great news for barbecue kings and beach bums but also for the weeds lurking below the surface of the soil popping up intermittently to strangle my carrots.

New research published in Cell describes another reason to cake ourselves in sun cream, cover up bare flesh and wear ridiculously wide-brimmed hats in the coming months: weed-like skin cancers which start below the surface of the skin and grow upwards.

"Too much sun" is well known to carry a risk of skin cancer. Prolonged exposure to the sun's Ultraviolet (UV) rays can wither the DNA in cells on the skin's surface sometimes causing multiple tumours to spring up at once.

Dr Bing Hu and colleagues found alarming evidence that some cancers may start much deeper in the tissue. This may explain why skin cancers frequently reappear: surgery may remove a tumour, but its roots may remain.

The new research suggests that skin cancer can be kick-started by changes in the dermis – deeper skin tissue where healthy cells reproduce to replenish the cells on the surface.

The root cause of certain skin
cancers may be much deeper in the
tissue than previously thought.

The team, from the University of Lausanne in Switzerland, discovered that UV light can cause mutations in the wiring of dermal cells, specifically to a protein called 'Notch' which is necessary for individual skin cells to communicate.

They found that mice born with malfunctioning Notch develop severely distorted skin full of lesions and tears. The dermal skin cells of these mice displayed accelerated cell division, a common prelude to tumour formation.

The mouse studies gave the team a vital clue of what to look for in human cells. They have since discovered Notch is disrupted in some human skin cancers too.

Dr Hu says that designing drugs to protect or repair Notch in human cells might be used in “preventing or reversing” the unseen effects of the sun on cells under our skin.

Until then, whether you're weeding, barbe-ing or bathing this summer the advice remains the same: enjoy responsibly. 

And remember to buy ice. And fire-lighters.

Reference:

Hu B, Castillo E, Harewood L, Ostano P, Reymond A, Dummer R, Raffoul W, Hoetzenecker W, Hofbauer GF, & Dotto GP (2012). Multifocal Epithelial Tumors and Field Cancerization from Loss of Mesenchymal CSL Signaling. Cell, 149 (6), 1207-20 PMID: 22682244

Faultless: Your skin's battle with open wounds and cancer

The San Andreas fault.
In our skin, fringes of cells meet to close a wound.
(picture credit: David Parker)

New research has revealed a connection between how our skin heals and the prevention of skin cancers.

In a paper published  two weeks ago in JCB, Jeremy Rotty and colleagues showed that keratin 6 (K6), a fibrous protein used to repair skin lesions, can also put the brakes on skin cells growing too quickly.

When the surface of your skin is scratched, the wound is quickly bridged by keratinocytes, cells full of K6 which migrate through the tissue and mesh together. Researchers found that K6, as well as providing scaffolding inside these cells, also attaches to and controls Src, a protein at the heart of the wiring for cell migration and growth.

It is here that a careful balance is struck. If there isn't enough Src activity inside a keratinocyte, it may not migrate at all, leaving wounds exposed. Too much Src, however, and the cells could migrate too far, growing into tumours. Skin cells lacking K6 to control Src activity have been shown to  produce aggressive cancers.

Keratinocytes actually roll into a wound
in the skin, like stones into a valley.
(picture credit: moonjazz)

The researchers from John Hopkins University, Baltimore, USA suggested that inside skin cancer cells K6 might be a “protective mechanism that maintains epithelial (skin surface) tumours in a ... less aggressive state".

What does this mean for me?

Future treatments for skin cancer might target the relationship between K6 and Src. A lack of K6 might also be looked for as a marker for predisposition to certain types of skin cancer.

What does this mean for science?

This is a great example of multi-tasking inside our cells. Keratin K6 can regulate both the structure and movement of keratinocytes. The relationship between K6 and Src  shows how important the inner-wiring of each individual cell can be to the overall tissue, where lesions need to be repaired despite the risk of cancer.

Reference:

Rotty, J., & Coulombe, P. (2012). A wound-induced keratin inhibits Src activity during keratinocyte migration and tissue repair The Journal of Cell Biology, 197 (3), 381-389 DOI: 10.1083/jcb.201107078