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Oncogenic ALKF1174L drives tumorigenesis in cutaneous squamous cell carcinoma

ABSTRACT: Oncogenic ALKF1174L drives tumorigenesis in cutaneous squamous cell carcinoma

PROVIDER: PRJNA615866 | ENA |

REPOSITORIES: ENA

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Oncogenic ALKF1174L drives tumorigenesis in cutaneous squamous cell carcinoma

Project description: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 is indispensable for 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.

2020-04-15 | GSE147642 | GEO

Oncogenic ALKF1174L drives tumorigenesis in cutaneous squamous cell carcinoma.

Project description: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.

| S-EPMC7184028 | biostudies-literature

Epigenome analysis of cutaneous squamous cell carcinoma samples

Project description:Genome wide DNA methylation profiling in cutaneous squamous cell carcinoma. The Infinium MethylationEPIC BeadChips 850K has been used to interrogate DNA methylation changes. The cohort included 23 patients in total, with precursors of squamous cell carcinoma (actinic keratosis group) and with cSCC at different stages.

2019-12-12 | E-MTAB-8542 | biostudies-arrayexpress

COL11A1 mutations in cutaneous squamous cell carcinoma [WES]

Project description:Whole exome sequencing was used to identify frequent COL11A1 mutations in cutaneous squamous cell carcinoma (cSCC).

2021-07-23 | GSE179296 | GEO

Differentially expressed miRNAs in human cutaneous squamous cell carcinoma

Project description:To determine the differentially expressed miRNAs in human cutaneous squamous cell carcinoma biopsies versus normal skin samples using microarray analysis.

2015-05-11 | E-MTAB-3409 | biostudies-arrayexpress

Sequencing Analysis of Cutaneous Squamous Cell Carcinoma

Project description:Sequencing Analysis of Cutaneous Squamous Cell Carcinoma

| PRJNA259586 | ENA

AK144841 in Cutaneous Squamous Cell Carcinoma (cSCC)

Project description:AK144841 in Cutaneous Squamous Cell Carcinoma (cSCC)

| PRJNA352422 | ENA

Characterisation of the adhesome of patient-derived cutaneous squamous carcinoma cells

Project description:Interactions between cells and the extracellular matrix, mediated by integrin adhesion complexes (IACs), play key roles in cancer progression and metastasis. We report here systems-level changes in the adhesome during progression of a patient-derived cutaneous squamous cell carcinoma (cSCC). We found that the actin regulatory protein Mena is enriched in IACs in metastatic cSCC cells and is connected within a subnetwork of actin-binding proteins to the LINC complex component nesprin-2.

2023-03-25 | PXD021492 | Pride

Targeted sequencing of localized and metastatic cutaneous squamous cell carcinoma

Project description:We report sequencing of 10 localized and 10 metastatic cutaneous squamous cell carcinomas from human subjects. Sequencing was done on an oncology targeted gene mutation panel consisting of 76 genes.

2020-07-15 | GSE150727 | GEO

Long non-coding RNAs in cutaneous squamous cell carcinoma

Project description:The expression of lncRNAs in cutaneous squamous cell carcinoma (cSCC) were determined with a commercially available microarray (Arraystar Inc.,Rockville, Maryland USA). The Arraystar human lncRNA Microarray V3.0 containing 30,586 LncRNAs and 26,109 coding transcripts (mRNAs)

2016-04-13 | GSE74859 | GEO

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