Dysregulated Expression of Phosphorylated Epidermal Growth Factor Receptor and Phosphatase and Tensin Homologue in Canine Cutaneous Papillomas and Squamous Cell Carcinomas

Persistent activation of the mammalian target of rapamycin signalling pathway in cutaneous squamous cell carcinomas in cats

“…18 Furthermore, we also showed that the persistent activation of EGFR may not be necessary for the activation of the mTOR signalling pathway, because some of the samples in which pS6 was detected were tumour samples in which EGFR was not activated. These findings are similar to those reported in human HNSCCs 18 and canine CSCCs, 9 which support the possible existence of EGFRindependent pathways that can stimulate the growth and survival of neoplastic cells. These results provide important information for the future development of target therapies for feline patients with CSCC, as they may provide the rationale of the use of mTOR inhibitors alone or in combination with EGFR inhibitors based on the activity of these signalling pathways in individual patients.…”

“…Among the complex network of signalling pathways that contribute to epidermal carcinogenesis, persistent activation of the phosphatidylinositol 3-kinase/ Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway has shown to be a frequent event in human and canine CSCC. [5][6][7][8][9] In addition, different murine models of skin carcinogenesis have shown that the PI3K/ Akt/mTOR signalling pathway represents a promising target for pharmacological intervention in CSCC. [10][11][12][13][14] The activation of the epidermal growth factor receptor (EGFR) leads to the activation of PI3K, which phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2), generating phosphatidylinositol [3][4][5]-trisphosphate (PIP3).…”

“…In normal conditions, the activity of the PI3K/Akt/mTOR signalling pathway is regulated by different negative feedback mechanisms, including the phosphatase and tensin homologue (PTEN), which interrupts PI3K signalling by dephosphorylating PIP3 to PIP2. 15 Although multiple molecular events may converge to promote the activation of the PI3K/Akt/mTOR signalling pathway in CSCC, [5][6][7][8][9] the status of activation of this signalling pathway in feline CSCC remains unknown.…”

“…Among the complex network of signalling pathways that contribute to epidermal carcinogenesis, persistent activation of the phosphatidylinositol 3‐kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway has shown to be a frequent event in human and canine CSCC 5–9 . In addition, different murine models of skin carcinogenesis have shown that the PI3K/Akt/mTOR signalling pathway represents a promising target for pharmacological intervention in CSCC 10–14 .…”

Alkannin exerts antitumor properties in cutaneous squamous cell carcinoma by inducing apoptosis and shifting the M1/M2 polarization of tumor‐associated macrophages by upregulating PTEN

“…Bai et al revealed that miR‐142‐5p induced CSCC stem cell‐like properties by hindering PTEN 18 . In addition, Sanz Ressel et al confirmed that PTEN content was reduced in CSCC 27 . Additionally, Gong et al revealed that miR‐221 modulated CSCC cell growth and the cell cycle by targeting PTEN 28 .…”