Activation of Src‐family tyrosine kinases in hyperproliferative epidermal disorders

Ayli, Elias E.; Li, Weijie; Brown, Tamu T.; Witkiewicz, Agnieszka K.; Elenitsas, Rosalie; Seykora, John T.

doi:10.1111/j.1600-0560.2007.00807.x

Cited by 47 publications

(46 citation statements)

References 13 publications

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“…SFK are known oncogenes 47 and can be downregulated by Srcasm 48. Increased activation of SFK and decreased Srcasm levels were reported in CSCC compared with unremarkable epidermis 27, 49, 50. It was later reported that the transgenic mice with elevated SFK activity spontaneously formed CSCC, and cutaneous neoplasia can be markedly inhibited by increasing Srcasm levels 27.…”

Section: Notch Signaling In Cutaneous Squamous Cell Carcinoma (Cscc)mentioning

confidence: 99%

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

et al. 2016

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The role of Notch pathway in tumorigenesis is highly variable. It can be tumor suppressive or pro‐oncogenic, typically depending on the cellular context. Squamous cell carcinoma (SCC) is a cancer of the squamous cell, which can occur in diverse human tissues. SCCs are one of the most frequent human malignancies for which the pathologic mechanisms remain elusive. Recent genomic analysis of diverse SCCs identified marked levels of mutations in NOTCH1, implicating Notch signaling pathways in the pathogenesis of SCCs. In this review, evidences highlighting NOTCH's role in different types of SCCs are summarized. Moreover, based on accumulating structural information of the NOTCH receptor, the functional consequences of NOTCH1 gene mutations identified from diverse SCCs are analyzed, emphasizing loss of function of Notch in these cancers. Finally, we discuss the convergent view on an intriguing possibility that Notch may function as tumor suppressor in SCCs across different tissues. These mechanistic insights into Notch signaling pathways will help to guide the research of SCCs and development of therapeutic strategies for these cancers.

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Section: Notch Signaling In Cutaneous Squamous Cell Carcinoma (Cscc)mentioning

confidence: 99%

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

et al. 2016

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“…SFKs, including Fyn, are regulators of cell proliferation, invasion, and metastasis and have been shown to play a role in the pathogenesis of cSCC (29,61,(63)(64)(65). Src-activating and signaling molecule (Srcasm) is a substrate and negative regulator of SFKs (66,67).…”

Section: Pathophysiologic Features Of Csccs Ras Family Members Of Prmentioning

confidence: 99%

From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma

Ratushny

Gober²,

Hick³

et al. 2012

J. Clin. Invest.

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489

477

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Cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer with over 250,000 new cases annually in the US and is second in incidence only to basal cell carcinoma. cSCC typically manifests as a spectrum of progressively advanced malignancies, ranging from a precursor actinic keratosis (AK) to squamous cell carcinoma (SCC) in situ (SCCIS), invasive cSCC, and finally metastatic SCC. In this Review we discuss clinical and molecular parameters used to define this range of cutaneous neoplasia and integrate these with the multiple experimental approaches used to study this disease. Insights gained from modeling cSCCs have suggested innovative therapeutic targets for treating these lesions.

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“…Invasive SCC is associated with UV-induced mutations in the p53 tumor suppressor gene, 4 Ras activation, NF-B blockade 5 and activation of Src family kinases. 6 However, these factors do not constitute a clear-cut cause or diagnostic or prognostic indicators of tumor aggressiveness. Consequently, there is a continuing need for the identification of target genes or pathways that are relevant to the molecular pathogenesis of SCC.…”

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confidence: 99%

The DNA Damage-Binding Protein XPC Is a Frequent Target for Inactivation in Squamous Cell Carcinomas

Feraudy

Ridd

Richards

et al. 2010

The American Journal of Pathology

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XPC, the main damage-recognition protein responsible for nucleotide excision repair of UVB damage to DNA, is lost or mutated in xeroderma pigmentosum group C (XP-C), a rare inherited disease characterized by high incidence and early onset of non-melanoma and melanoma skin cancers. The high incidence of skin cancers in XP-C patients suggests that loss of expression of XPC protein might also provide a selective advantage for initiation and progression of similar cancers in non XP-C patients in the general population. To test whether XPC is selectively lost in squamous cell carcinomas from non XP-C patients, we examined XPC expression by immunohistochemistry on a tissue microarray with 244 tissue cores, including in situ and invasive squamous-cell carcinomas (SCCs), keratoacanthoma (KA), and normal skin samples from both immunocompetent and immunosuppressed patients. We found that XPC expression was lost in 49% of invasive squamous cell carcinomas from immunocompetent patients and 59% from immunosuppressed patients. Loss of expression was correlated with deletions of chromosomal 3p and mutations in the XPC gene. The XPC gene is consequently inactivated or lost in almost half of squamous cell carcinomas from non XP-C patients. Loss or mutation of XPC may be an early event during skin carcinogenesis that provides a selective advantage for initiation and progression of squamous cell carcinomas in

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Activation of Src‐family tyrosine kinases in hyperproliferative epidermal disorders

Abstract: This study shows increased staining of activated SFKs in human biopsy specimens of psoriasis and cutaneous neoplasia. These data provide direct evidence for increased activation of SFKs in the pathogenesis of hyperproliferative epidermal disorders.

Cited by 47 publications

References 13 publications

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

Does Notch play a tumor suppressor role across diverse squamous cell carcinomas?

From keratinocyte to cancer: the pathogenesis and modeling of cutaneous squamous cell carcinoma

The DNA Damage-Binding Protein XPC Is a Frequent Target for Inactivation in Squamous Cell Carcinomas

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