The importance of the PI3K/AKT/mTOR signaling pathway in canine neoplasms: Literature review

Ferreira, M. G. P. A.; Filho, NP Reis; Pascoli, AL; Arosti, BM; Pazzini, JM; Huppes, Rafael; Nardi, AB de; Tinucci‐Costa, Mirela; Laufer-Amorim, Renée

doi:10.4067/s0301-732x2016000200002

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…Additionally, in the current study, most of the changed pathways are related to animal immunology; therefore, the low immune capacity of Nile tilapia under hypersaline stress might be an outcome of these responsive pathways. Furthermore, the PI3K-Akt signaling pathway, the least significantly changed pathway, is one of the most actively studied kinase pathways as it plays an integral role in mediating signals for cell growth, survival, cell-cycle progression, differentiation, transcription, translation, and glucose metabolism in animals (Yao et al, 2014 ; Ferreira et al, 2016 ; Li et al, 2017 ). Therefore, the downregulation of this pathway could be the reason for slowed growth of Nile tilapia under hypersaline conditions (Gan et al, 2016 ), since fish require more energy during normal growth for osmoregulation and icon homeostasis (Tseng and Hwang, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

Brain Transcriptome Profiling Analysis of Nile Tilapia (Oreochromis niloticus) Under Long-Term Hypersaline Stress

Liu

et al. 2018

Front. Physiol.

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The fish brain plays an important role in controlling growth, development, reproduction, and adaptation to environmental change. However, few studies stem from the perspective of whole transcriptome change in a fish brain and its response to long-term hypersaline stress. This study compares the differential transcriptomic responses of juvenile Nile tilapia (Oreochromis niloticus) maintained for 8 weeks in brackish water (16 practical salinity units, psu) and in freshwater. Fish brains from each treatment were collected for RNA-seq analysis to identify potential genes and pathways responding to hypersaline stress. A total of 27,089 genes were annotated, and 391 genes were expressed differently in the salinity treatment. Ten pathways containing 40 differentially expressed genes were identified in the tilapia brain. Antigen processing and presentation and phagosome were the two principally affected pathways in the immune system. Thirty-one of 40 genes were involved in various expressions associated with environmental information processing pathways such as neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction, the Jak-STAT signaling pathway, cell adhesion molecules (CAMs), and the PI3K-Akt signaling pathway, which are the upstream pathways for modulation of immunity and osmoregulation. The most-changed genes (>5-fold) were all down-regulated, including four growth hormone/prolactin gene families, i.e., prolactin precursor (−10.62), prolactin-1 (−11), somatotropin (−10.15), somatolactin-like (−6.18), and two other genes [thyrotropin subunit beta (−7.73) and gonadotropin subunit beta-2 (−5.06)] that stimulated prolactin release in tilapia. The downregulation pattern of these genes corroborates the decrease in tilapia immunity with increasing salinity and reveals an adaptive mechanism of tilapia to long-term hypersaline stress. Ovarian steroidogenesis, isoquinoline alkaloid biosynthesis, and phenylalanine metabolism are the three important pathways in the response of the fish to long-term hypersaline stress. This study has identified several pathways and relevant genes that are involved in salinity regulation in a euryhaline fish and provides insight into understanding regulatory mechanisms of fish to salinity change.

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Section: Discussionmentioning

confidence: 99%

Brain Transcriptome Profiling Analysis of Nile Tilapia (Oreochromis niloticus) Under Long-Term Hypersaline Stress

Liu

et al. 2018

Front. Physiol.

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“…The PI3K/AKT/mTOR pathway is related to proliferation, protein synthesis, survival, angiogenesis, apoptosis, and cell motility (Ferreira et al., 2016; Kim et al., 2020). PI3K activates Akt, which in turn resulted in the phosphorylation and activation of mTOR (Chen, Li, et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Grape seed proanthocyanidin extract ameliorates cisplatin‐induced testicular apoptosis via PI3K/Akt/mTOR and endoplasmic reticulum stress pathways in rats

et al. 2021

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Testicular toxicity is an adverse reaction of the effective chemotherapy drug cisplatin (CIS). Our previous study found that grape seed proanthocyanidin extract (GSPE) had a protective effect on CIS‐induced testicular toxicity. However, the protective mechanism of GSPE against CIS‐induced testicular toxicity remains unknown. In this study, we aimed to investigate whether GSPE can reduce CIS‐induced testicular toxicity and its potential mechanism in rats. The results showed that GSPE ameliorated CIS‐induced the apoptosis of testicular cells and inhibited the protein levels of Bad, Cyt c, caspase‐9, caspase‐3, caspase‐12, GRP78, CHOP, IRE1α, p‐IRE1α, XBP‐1S, PERK, p‐PERK, eIF2α, and p‐eIF2α. Besides, GSPE reversed the downregulation of PI3K, p‐PI3K, Akt, p‐Akt, mTOR, and p‐mTOR protein expression induced by CIS. These results indicated that GSPE can improve CIS‐induced testicular cells apoptosis via activating PI3K/Akt/mTOR and inhibiting Bad/Cyt c/caspase‐9/caspase‐3 pathways. And GSPE relieved endoplasmic reticulum stress‐mediated apoptosis via inhibiting PREK/eIF2α and IRE1α/XBP‐1S/caspase‐12 pathways. In conclusion, the evidence suggested that GSPE can act as a protective agent against testicular toxicity induced by CIS. Practical applications Testicular toxicity was a well‐known adverse effect of cisplatin (CIS) in cancer treatment. Grape seed proanthocyanidin extract (GSPE) has been reported to serve as one of the most therapeutic potentials agents. In present study, we explored the regulatory effects of GSPE on the apoptosis induced by CIS, which involved testicular apoptosis mechanisms in rats. Our results indicated that CIS caused testicular toxicity via PI3K/AKT/mTOR and ERS mediated apoptosis pathway in rats. This toxicity was attenuated by GSPE treatment via activated PI3K/Akt/mTOR pathway, and inhibiting Bad/CytC/caspase‐9/caspase‐3 as well as PREK/eIF2α, IRE1α/XBP‐1S/caspase‐12 pathways. Our findings suggest that GSPE may be a novel protective agent against testicular toxicity induced by CIS.

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“…This parallel approach could bring new perspectives regarding risk factors and experimental paradigms from which both species will benefit. For instance, activation of the mTOR signaling pathway has been also explored in canine melanoma as well as in the human disease, and studies in canine melanoma cell lines have demonstrated activation of this pathway along with the inhibitory efficacy of Rapamycin and other drugs (71)(72)(73). Clearly there is much to be learned about the genetic drivers of melanoma in dogs.…”

Section: Lessons For Canine Melanoma?mentioning

confidence: 99%

Canine melanoma: A review of diagnostics and comparative mechanisms of disease and immunotolerance in the era of the immunotherapies

et al. 2023

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Melanomas in humans and dogs are highly malignant and resistant to therapy. Since the first development of immunotherapies, interest in how the immune system interacts within the tumor microenvironment and plays a role in tumor development, progression, or remission has increased. Of major importance are tumor-infiltrating lymphocytes (TILs) where distribution and cell frequencies correlate with survival and therapeutic outcomes. Additionally, efforts have been made to identify subsets of TILs populations that can contribute to a tumor-promoting or tumor-inhibiting environment, such as the case with T regulatory cells versus CD8 T cells. Furthermore, cancerous cells have the capacity to express certain inhibitory checkpoint molecules, including CTLA-4, PD-L1, PD-L2, that can suppress the immune system, a property associated with poor prognosis, a high rate of recurrence, and metastasis. Comparative oncology brings insights to comprehend the mechanisms of tumorigenesis and immunotolerance in humans and dogs, contributing to the development of new therapeutic agents that can modulate the immune response against the tumor. Therapies that target signaling pathways such as mTOR and MEK/ERK that are upregulated in cancer, or immunotherapies with different approaches such as CAR-T cells engineered for specific tumor-associated antigens, DNA vaccines using human tyrosinase or CGSP-4 antigen, anti-PD-1 or -PD-L1 monoclonal antibodies that intercept their binding inhibiting the suppression of the T cells, and lymphokine-activated killer cells are already in development for treating canine tumors. This review provides concise and recent information about diagnosis, comparative mechanisms of tumor development and progression, and the current status of immunotherapies directed toward canine melanoma.

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The importance of the PI3K/AKT/mTOR signaling pathway in canine neoplasms: Literature review

Cited by 5 publications

References 29 publications

Brain Transcriptome Profiling Analysis of Nile Tilapia (Oreochromis niloticus) Under Long-Term Hypersaline Stress

Brain Transcriptome Profiling Analysis of Nile Tilapia (Oreochromis niloticus) Under Long-Term Hypersaline Stress

Grape seed proanthocyanidin extract ameliorates cisplatin‐induced testicular apoptosis via PI3K/Akt/mTOR and endoplasmic reticulum stress pathways in rats

Canine melanoma: A review of diagnostics and comparative mechanisms of disease and immunotolerance in the era of the immunotherapies

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