KRAS mutation is associated with elevated myeloblastin activity in human lung adenocarcinoma.
Lung cancer is the leading cause of all cancer deaths worldwide with suboptimal prognosis and treatment options. Therefore this study aimed to identify molecular characteristics with a predictive clinical utility which at the same time might represent novel therapeutic targets for human lung adenocarcinoma. Within this study mutations of v-Ki-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS), a gene frequently mutated in lung adenocarcinoma, and their association with enzymatic activities, as assessed by activity-based proteomics, of members of the serine hydrolase (SH) superfamily, a large class of enzymes that have previously been linked to cancer was investigated. The results revealed that the activity of myeloblastin was significantly altered in the lung adenocarcinoma biopsies harboring a KRAS gene mutation. In conclusion myeloblastin is a potential therapeutic target for human lung adenocarcinoma, indicating that the combination of activity-based proteomics with mutational analysis is a valid approach for the discovery of novel biomarkers.
Division of Thoracic Surgery, Institute of Surgical Pathology, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland. thomas.wiedl@yahoo.com
Thomas
T
Wiedl
Stéphane
S
Collaud
Sven
S
Hillinger
Stephan
S
Arni
Chris
C
Burgess
Werner
W
Kroll
Peter
P
Schraml
Alex
A
Soltermann
Holger
H
Moch
Walter
W
Weder
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004789:Enzyme Activation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053146:Myeloblastin / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D053146:Myeloblastin; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins