Exploiting the origins of Ras mediated squamous cell carcinoma to develop novel therapeutic interventions. - PubMed - NCBI
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Search: Exploiting[Title] AND origins[Title] AND Ras[Title] AND mediated[Title] AND squamous[Title] AND cell[Title] AND carcinoma[Title] AND develop[Title] AND novel[Title] AND therapeutic[Title] AND interventions[Title]
Small GTPases. 2011 Nov 1;2(6):318-321.
Exploiting the origins of Ras mediated squamous cell carcinoma to develop novel therapeutic interventions.
White AC1, Lowry WE.
Department of Molecular, Cell and Developmental Biology; Jonsson Comprehensive Cancer Center; Eli and Edythe Broad Center for Stem Cell Research; Molecular Biology Institute; University of California, Los Angeles; Los Angeles, CA USA.
The small GTPase Ras is activated in a high proportion of human cancers. Attempts to clinically block Ras activity through pharmacological means has proven largely ineffective thus far. We employed an inducible mouse model of squamous cell carcinoma (SCC) to study the effect of Ras activation and show that hair follicle stem cells (HFSCs) are a cell of origin for SCC, whereas their more restricted progeny cannot serve as cancer cells of origin and are refractory to Ras activation. We propose that by identifying the unique mechanisms by which HFSCs are mobilized to initiate Ras mediated tumorigenesis, the molecular process behind SCC can be more completely elucidated and context dependent activities for Ras more clearly defined. Here, we summarize our recent results and point to future experiments designed to create novel therapeutics by exploiting the differential sensitivities of various cells within the epidermis to Ras activation.
PMC3337161
10.4161/sgtp.18088
Figure 1. Ras signaling pathways examined in SCC prone KrasG12D induced hair follicle stem cells and in SCC resistant KrasG12D induced hair follicle transit amplifying cells. P-Erk, p-Akt, p-S6 and p-p38 stained hair follicle hyperplasia and cyst structures at high levels when KrasG12D was induced in hair follicle stem cells. P-mTor, p-Ikkα/β and p-NFκB were also present, albeit at lower levels. In contrast, only p-p38 was found in the Shh-expressing hair follicle transit amplifying cells following KrasG12D induction. Darker shadings of gray represent higher activity levels. (Image adapted from White et al.15).
Exploiting the origins of Ras mediated squamous cell carcinoma to develop novel therapeutic interventions
Exploiting[Title] AND origins[Title] AND Ras[Title] AND mediated[Title] AND squamous[Title] AND cell[Title] AND carcinoma[Title] AND develop[Title] AND novel[Title] AND therapeutic[Title] AND interventions[Title]
Exploiting the origins of Ras mediated squamous cell carcinoma to develop novel therapeutic interventions. - PubMed - NCBI
Search: Exploiting the origins of Ras mediated squamous cell carcinoma...
Search: Exploiting[Title] AND origins[Title] AND Ras[Title] AND mediated[Title] AND squamous[Title] AND cell[Title] AND carcinoma[Title] AND develop[Title] AND novel[Title] AND therapeutic[Title] AND interventions[Title]
Small GTPases. 2011 Nov 1;2(6):318-321.
Exploiting the origins of Ras mediated squamous cell carcinoma to develop novel therapeutic interventions.
White AC1, Lowry WE.
Department of Molecular, Cell and Developmental Biology; Jonsson Comprehensive Cancer Center; Eli and Edythe Broad Center for Stem Cell Research; Molecular Biology Institute; University of California, Los Angeles; Los Angeles, CA USA.
The small GTPase Ras is activated in a high proportion of human cancers. Attempts to clinically block Ras activity through pharmacological means has proven largely ineffective thus far. We employed an inducible mouse model of squamous cell carcinoma (SCC) to study the effect of Ras activation and show that hair follicle stem cells (HFSCs) are a cell of origin for SCC, whereas their more restricted progeny cannot serve as cancer cells of origin and are refractory to Ras activation. We propose that by identifying the unique mechanisms by which
 HFSCs are mobilized to initiate Ras mediated tumorigenesis, the molecular process behind SCC can be more completely elucidated and context dependent activities for Ras more clearly defined. Here, we summarize our recent results and point to future experiments designed to create novel therapeutics by exploiting the differential sensitivities of various cells within the epidermis to Ras activation.
PMC3337161
10.4161/sgtp.18088
Figure 1. Ras signaling pathways examined in SCC prone KrasG12D induced hair follicle stem cells and in SCC resistant KrasG12D induced hair follicle transit amplifying cells. P-Erk, p-Akt, p-S6 and p-p38 stained hair follicle hyperplasia and cyst structures at high levels when KrasG12D was induced in hair follicle stem cells. P-mTor, p-Ikkα/β and p-NFκB were also present, albeit at lower levels. In contrast, only p-p38 was found in the Shh-expressing hair follicle transit amplifying cells following KrasG12D induction. Darker shadings of gray represent higher activity levels. (Image adapted from White et al.15).
Exploiting the origins of Ras mediated squamous cell carcinoma to develop novel therapeutic interventions
Exploiting[Title] AND origins[Title] AND Ras[Title] AND mediated[Title] AND squamous[Title] AND cell[Title] AND carcinoma[Title] AND develop[Title] AND novel[Title] AND therapeutic[Title] AND interventions[Title]