Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

05 Mar 2017 - 09 Mar 2017
20 Mar 2017 - 23 Mar 2017
12 Apr 2017 - 14 Apr 2017

Enzyme Responsible for Skin Thickening Disorder Linked to Esophageal Cancer

By BiotechDaily International staff writers
Posted on 17 Feb 2017
Image: A photomicrograph of keratin filaments inside cells (Photo courtesy of Wikimedia Commons).
Image: A photomicrograph of keratin filaments inside cells (Photo courtesy of Wikimedia Commons).
A recent paper explained the molecular mechanism underlying the development of palmoplantar keratoderma (thickening of the skin on the palms of the hands and soles of the feet) in the rare genetic disease Tylosis with esophageal cancer (TOC).

This condition is inherited as an autosomal dominant syndrome and is characterized by palmoplantar keratoderma, oral precursor lesions particularly on the gums (leukoplakia), and a high lifetime risk of esophageal cancer (95% develop esophageal cancer by the age of 65).

Investigators at Queen Mary University of London reported in the January 27, 2017, online edition of the journal Nature Communications, that the inactive rhomboid protease RHBDF2 (Rhomboid family member 2 - the alternative name iRhom2 has been proposed, in order to clarify that it is a catalytically inactive member of the rhomboid family of intramembrane serine proteases) regulates thickening of the footpad epidermis through its interaction with keratin 16 (K16). K16 is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad, which can be induced in hyperproliferative states such as wound healing, inflammation, and cancer.

The investigators found that mice that had been genetically engineered to lack the iRHOM2 gene had abnormally thin paw skin, while humans with mutations that increased the expression of iRHOM2 had thickened palms and soles with callouses, and that a high percentage of these patients developed esophageal cancer.

At the molecular level, the investigators found that iRHOM2 bound to K16, and that this interaction was increased in TOC keratinocytes, where it was associated with robust downregulation of K16’s binding partner K6. In humans and mice, iRHOM2 loss resulted in dampened proliferation and reduced K16 expression, and in mice this led to thinning of epidermis in the footpad.

The authors concluded that, "These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this "stress" keratin is regulated. These findings highlight a novel and fundamental role for iRHOM2 in regulating the epithelial response to mechanical stress."


Channels

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Business

view channel

Collaborative Agreement to Aid in Setting Guidelines for Evaluating Potential Ebola Therapy

Cooperation between an Israeli biopharmaceutical company and medical branches of the US government is designed to set ground rules for continued evaluation of an experimental therapy for Ebola virus disease. RedHill Biopharma Ltd. (Tel Aviv, Israel), a biopharmaceutical company primarily focused on development and c... Read more
Copyright © 2000-2017 Globetech Media. All rights reserved.