Abstract 1506: Frequent loss of function mutations in TGFβR1 and TGFβR2 identify hair follicle bulge stem cells as the cell of origin for cutaneous squamous cell carcinoma

2015 ◽  
Author(s):  
Patrizia Cammareri ◽  
Aidan M. Rose ◽  
David F. Vincent ◽  
Silvana Libertini ◽  
Rachel A. Ridgway ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Hair Follicle ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Cell Of Origin ◽  
Loss Of Function

scholarly journals Sox9 expression in canine epithelial skin tumors

2015 ◽  
Vol 59 (3) ◽  
Author(s):  
E. Fantinato ◽  
L. Milani ◽  
G. Sironi
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Hair Follicle ◽  
Squamous Cell ◽  
Expression Patterns ◽  
Regulatory Gene ◽  
Skin Neoplasms ◽  
Stem Cell Marker ◽  
Molecular Characteristics

<p><em>Sox9</em> is a master regulatory gene involved in developmental processes, stem cells maintenance and tumorigenesis. This gene is expressed in healthy skin but even in several skin neoplasms, where its expression patterns often resembles those of the developing hair follicle. In this study, samples from eleven different types of canine skin neoplasms (squamous papilloma, squamous cell carcinoma, infundibular keratinizing acanthoma, inferior tricholemmoma, isthmic tricholemmoma, trichoblastoma, trichoepitelioma, malignant trichoepitelioma, pilomatricoma, subungual keratoacanthoma, subungual squamous cell carcinoma) were immunohistochemically stained and evaluated for <em>Sox9</em> with the aim to correlate tumor phenotype with molecular characteristics that may help to better define tumor development, contribute to its diagnosis and clinical management. Keratoacanthoma excluded, all the skin neoplasms examined showed a variable positivity to <em>Sox9</em>, especially in the basal layers, but with major intensity in neoplasms developing from the bulge region of the hair follicle, as trichoblastoma. According to our results, <em>Sox9</em> could be employed as a stem cell marker to better assess the role of stem cells in canine epidermal and follicular tumors.</p>

scholarly journals Deletion of p53 and Hyper-Activation of PIK3CA in Keratin-15+ Stem Cells Lead to the Development of Spontaneous Squamous Cell Carcinoma

2020 ◽  
Vol 21 (18) ◽  
pp. 6585
Author(s):  
Samantha M. Y. Chen ◽  
Bian Li ◽  
Andrew G. Nicklawsky ◽  
Alexandra L. Krinsky ◽  
Tonya Brunetti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Model ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Loss Of Function

Squamous cell carcinoma (SCC) is the second commonest type of skin cancer, and SCCs make up about 90% of head and neck cancers (HNSCCs). HNSCCs harbor two frequent molecular alterations, namely, gain-of-function alterations of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and loss-of-function mutations of tumor protein p53 (TP53). However, it remains poorly understood whether HNSCCs harboring different genetic alterations exhibit differential immune tumor microenvironments (TME). It also remains unknown whether PIK3CA hyperactivation and TP53 deletion can lead to SCC development spontaneously. Here, we analyzed the Cancer Genome Atlas (TCGA) datasets of HNSCCs and found that patients with both PIK3CA and TP53 alterations exhibited worse survival, significantly lower CD8 tumor infiltrating lymphocytes (TILs) and higher M0 macrophages than other controls. To better model human tumorigenesis, we deleted TP53 and constitutively activated PIK3CA in mouse keratin-15-expressing stem cells, which leads to the spontaneous development of multilineage tumors including SCCs, termed Keratin-15-p53-PIK3CA (KPPA) tumors. KPPA tumors were heavily infiltrated with myeloid-derived suppressor cells (MDSCs), with a drastically increased ratio of polymorphonuclear-MDSC (PMN-MDSC) versus monocytic-MDSC (M-MDSC). CD8 TILs expressed more PD-1 and reduced their polyfunctionality. Overall, we established a genetic model to mimic human HNSCC pathogenesis, manifested with an immunosuppressive TME, which may help further elucidate immune evasion mechanisms and develop more effective immunotherapies for HNSCCs.

scholarly journals Cancer Stem Cells in Head and Neck Cutaneous Squamous Cell Carcinoma Express Cathepsins

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Therese Featherston ◽  
Helen D. Brasch ◽  
Sam D. Siljee ◽  
Bede van Schaijik ◽  
Josie Patel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cancer Stem Cells ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma

scholarly journals Oncogenic ALKF1174L drives tumorigenesis in cutaneous squamous cell carcinoma

2020 ◽  
Vol 3 (6) ◽  
pp. e201900601
Author(s):  
Marco Gualandi ◽  
Maria Iorio ◽  
Olivia Engeler ◽  
André Serra-Roma ◽  
Giuseppe Gasparre ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Cell Of Origin ◽  
Anaplastic Lymphoma ◽  
Downstream Effector ◽  
Tumorigenic Potential ◽  
Common Skin ◽  
First Time

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer characterized by increased mortality. Here, we show for the first time that anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase of the insulin receptor superfamily, plays a pivotal role in the pathogenesis of cSCC. Our data demonstrate that the overexpression of the constitutively active, mutated ALK, ALKF1174L, is sufficient to initiate the development of cSCC and is 100% penetrant. Moreover, we show that cSCC development upon ALKF1174L overexpression is independent of the cell-of-origin. Molecularly, our data demonstrate that ALKF1174L cooperates with oncogenic KrasG12D and loss of p53, well-established events in the biology of cSCC. This cooperation results in a more aggressive cSCC type associated with a higher grade histological morphology. Finally, we demonstrate that Stat3 is a key downstream effector of ALKF1174L and likely plays a role in ALKF1174L-driven cSCC tumorigenesis. In sum, these findings reveal that ALK can exert its tumorigenic potential via cooperation with multiple pathways crucial in the pathogenesis of cSCC. Finally, we show that human cSCCs contain mutations in the ALK gene. Taken together, our data identify ALK as a new key player in the pathogenesis of cSCC, and this knowledge suggests that oncogenic ALK signaling can be a target for future clinical trials.

scholarly journals MiR-199a-5p represses the stemness of cutaneous squamous cell carcinoma stem cells by targeting Sirt1 and CD44ICD cleavage signaling

Cell Cycle ◽  
2019 ◽  
Vol 19 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Ruo-Huang Lu ◽  
Zhi-Qiang Xiao ◽  
Jian-Da Zhou ◽  
Chao-Qi Yin ◽  
Zi-Zi Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma

scholarly journals Ginsenoside Rh2 Inhibits Cancer Stem-Like Cells in Skin Squamous Cell Carcinoma

2015 ◽  
Vol 36 (2) ◽  
pp. 499-508 ◽  
Author(s):  
Shunli Liu ◽  
Mingrui Chen ◽  
Pengcheng Li ◽  
Yujia Wu ◽  
Chunjuan Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cancer Stem Cells ◽  
Cell Viability ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Ginsenoside Rh2 ◽  
Loss Of Function ◽  
Tumor Sphere ◽  
Skin Squamous Cell Carcinoma

Background/Aims: Treatments targeting cancer stem cells (CSCs) are most effective cancer therapy, whereas determination of CSCs is challenging. We have recently reported that Lgr5-positive cells are cancer stem cells (CSCs) in human skin squamous cell carcinoma (SCC). Ginsenoside Rh2 (GRh2) has been shown to significantly inhibit growth of some types of cancers, whereas its effects on the SCC have not been examined. Methods: Here, we transduced human SCC cells with lentivirus carrying GFP reporter under Lgr5 promoter. The transduced SCC cells were treated with different doses of GRh2, and then analyzed cell viability by CCK-8 assay and MTT assay. The effects of GRh2 on Lgr5-positive CSCs were determined by fow cytometry and by tumor sphere formation. Autophagy-associated protein and β-catenin were measured by Western blot. Expression of short hairpin small interfering RNA (shRNA) for Atg7 and β-catenin were used to inhibit autophagy and β-catenin signaling pathway, respectively, as loss-of-function experiments. Results: We found that GRh2 dose-dependently reduced SCC viability, possibly through reduced the number of Lgr5-positive CSCs. GRh2 increased autophagy and reduced β-catenin signaling in SCC cells. Inhibition of autophagy abolished the effects of GRh2 on β-catenin and cell viability, while increasing β-catenin abolished the effects of GRh2 on autophagy and cell viability. Conclusion: Taken together, our data suggest that GRh2 inhibited SCC growth, possibly through reduced the number of Lgr5-positive CSCs. This may be conducted through an interaction between autophagy and β-catenin signaling.

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