The secretome of skin cancer cells activates the mTOR/MYC pathway in healthy keratinocytes and induces tumorigenic properties.
Cutaneous squamous cell carcinoma (cSCC) is the most prominent tumor of non-melanoma skin cancers and the most aggressive tumor among keratinocyte carcinoma of the skin, showing a high potential for local invasion and metastasis. The cSCC incidences increased dramatically in recent years and the disease occurs more commonly than any other malignancy. The secretome of cancer cells is currently the focus of many studies in order to identify new marker proteins for different types of cancer and to investigate its influence on the tumor microenvironment. In our study we evaluated whether the secretome of cSCC cells has an impact on keratinocytes, the surrounding tissue cells of cSCC. Therefore, we analyzed and compared the secretome of human A431 cancer cells and of HaCaT keratinocytes by mass spectrometry. In a second experiment, keratinocytes were exposed to the secretome of A431 cells and vice versa and the transcriptome was analyzed by next-generation sequencing. HaCaT cells incubated with A431 conditioned medium revealed a significantly activated mammalian target of rapamycin pathway with a concomitant increase in proliferation and migration. In conclusion, our data demonstrate the impact of the secretome of cancer cells on the transcription machinery of the cells surrounding the tumor, leading to a tumorigenic cell fate.
['Hoesl|Christine|C|', 'Zanuttigh|Enrica|E|', 'Fröhlich|Thomas|T|', 'Philippou-Massier|Julia|J|', 'Krebs|Stefan|S|', 'Blum|Helmut|H|', 'Dahlhoff|Maik|M|']
D017209:Apoptosis D063646:Carcinogenesis D002294:Carcinoma, Squamous Cell D002453:Cell Cycle D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D015972:Gene Expression Regulation, Neoplastic D006801:Humans D015603:Keratinocytes D020543:Proteome D016271:Proto-Oncogene Proteins c-myc D015398:Signal Transduction D012867:Skin D012878:Skin Neoplasms D058570:TOR Serine-Threonine Kinases D059467:Transcriptome D059016:Tumor Microenvironment
Secretome mTOR Keratinocytes Squamous cell carcinoma Transcriptome