The genetic evolution of skin squamous cell carcinoma: tumor suppressor identity matters

Missero, Caterina

doi:10.1111/exd.13075

Cited by 6 publications

(7 citation statements)

References 25 publications

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“…Skin squamous cell carcinoma (SCC), as one of the second most frequent cutaneous carcinomas, often contributing to the development of benign lesions called actinic keratosis (Missero, 2016). Chronic exposure to ultraviolet (UV) radiation is the leading etiologic factor of skin SCC, and other known causes include arsenic exposure, ionizing radiation, and history of nonmelanoma skin cancer (Phillips et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Retracted: Gadd45a gene silencing by RNAi promotes cell proliferation and inhibits apoptosis and senescence in skin squamous cell carcinoma through the p53 signaling pathway

Liu

Tian

Xiong

et al. 2018

Journal Cellular Physiology

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Skin squamous cell carcinoma (SCC) is generally considered as nonaggressive lesions and mainly caused by ultraviolet (UV) radiation. Gadd45a is a key component protecting skin against UV-induced tumors. For that, the study aims to investigate the mechanism of Gadd45a gene silencing on cell proliferation, apoptosis, and senescence in nude mice with skin SCC through the p53 signaling pathway. Healthy nude mice was collected as the normal group and 40 nude mouse models of skin SCC were successfully established as the model group, which were sub-divided into five groups. The incidence, size, and weight of SCC tumor of nude mice were observed. The mRNA expression of Gadd45a, Cyclin B1, MMP-2, Bcl-2, and Bax were determined by RT-qPCR. Cell viability, cell cycle and apoptosis, cell senescence were detected by MTT assay, flow cytometry, and β-galactosidase staining, respectively. The levels of inflammatory factors and vascular endothelial growth factor (VEGF) were detected by using ELISA. The protein expression rate of mutant p53 was detected by immunohistochemistry. Mice transfected with siGadd45a showed increased tumor incidence, size, and weight. Cells transfected with siGadd45a showed decrease in expression of Gadd45a and Bax; and increase in expression of Cyclin B1, MMP-2, and Bcl-2, expression of mutant p53, IL-1α, IL-1β, IL-6, TNF-α, and VEGF. Cell apoptosis and senescence were inhibited, while cell viability and proliferation were promoted after siGadd45a treatment. The results reveal that Gadd45a silencing increases tumor cell proliferation and reduces apoptosis and senescence through the p53 signaling pathway in skin SCC.

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Section: Introductionmentioning

confidence: 99%

Retracted: Gadd45a gene silencing by RNAi promotes cell proliferation and inhibits apoptosis and senescence in skin squamous cell carcinoma through the p53 signaling pathway

Liu

Tian

Xiong

et al. 2018

Journal Cellular Physiology

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“…Cutaneous squamous cell carcinoma (cSCC), the second most frequent skin cancer, often arises from the progression of benign lesions [ 1 ]. This progression is believed to be due to sequential DNA mutations in oncogenes and tumor suppressor genes including TP53, NOTCH1 and CDKN2A [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Hmga2 translocation induced in skin tumorigenesis

Boland

et al. 2017

Oncotarget

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Hmga2 protein, a transcription factor involved in chromatin architecture, is expressed chiefly during development, where it has many key biological functions. When expressed in adult tissues from in various organs, Hmga2 is always related to cancer development. The role of Hmga2 in skin tumorigenesis is, however, not yet understood. We demonstrated that Hmga2 can be found in non-transformed epidermis, specifically located to the membrane of keratinocytes (KCs) in epidermis. Ex vivo culture of KCs and development of skin carcinomas in DMBA and TPA mouse models was associated with translocation of the Hmga2 protein from the membrane into the nucleus, where Hmga2 induced its own expression by binding to the Hmga2 promoter. Panobinostat, an HDAC inhibitor, downregulated Hmga2 expression by preventing Hmga2 to bind its own promoter, and thus inhibiting Hmga2 promoter activity. Hmga2 translocation to the nucleus could in part be prevented by an inhibitor for ROCK1. Our findings demonstrate that upon program of benign papilloma to malignant cSCC of skin tumorigenesis, Hmga2 translocates in a ROCK-dependent manner from the membrane to the nucleus, where it serves as an autoregulatory transcription factor, causing cell transformation.

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“…Similar to melanoma, KRAS is found to be mutated in skin squamous cell carcinoma but at a low rate. In fact, many mouse models of cutaneous squamous cell carcinoma take advantage of inducible mutations in KRAS along with mutations of specific tumor suppressor genes [83]. There has been a great deal of progress in targeting downstream effector proteins of KRAS for the treatment of melanoma.…”

Section: Skin Cancermentioning

confidence: 99%

Targeting KRAS in Cancer: Promising Therapeutic Strategies

Mustachio

Chelariu-Raicu

Székvölgyi

et al. 2021

Cancers

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The Kirsten rat sarcoma viral oncogene homolog (KRAS) is mutated in approximately 25% of all human cancers and is known to be a major player promoting and maintaining tumorigenesis through the RAS/MAPK pathway. Over the years, a large number of studies have identified strategies at different regulatory levels to tackle this ‘difficult-to-target’ oncoprotein. Yet, the most ideal strategy to overcome KRAS and its downstream effects has yet to be uncovered. This review summarizes the role of KRAS activating mutations in multiple cancer types as well as the key findings for potential strategies inhibiting its oncogenic behavior. A comprehensive analysis of the different pathways and mechanisms associated with KRAS activity in tumors will ultimately pave the way for promising future work that will identify optimum therapeutic strategies.

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The genetic evolution of skin squamous cell carcinoma: tumor suppressor identity matters

Cited by 6 publications

References 25 publications

Retracted: Gadd45a gene silencing by RNAi promotes cell proliferation and inhibits apoptosis and senescence in skin squamous cell carcinoma through the p53 signaling pathway

Retracted: Gadd45a gene silencing by RNAi promotes cell proliferation and inhibits apoptosis and senescence in skin squamous cell carcinoma through the p53 signaling pathway

Hmga2 translocation induced in skin tumorigenesis

Targeting KRAS in Cancer: Promising Therapeutic Strategies

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