Cancer Therapy and Oncology International Journal (CTOIJ)

Permissive Changes in Consequential Carcinogenesis as Integral Deactivation of Pi3k Pathways, In Terms of the Single Oncogenic Transformation Step

Lawrence M Agius*

Department of pathology, University of Malta Medical School, Malta

Submission: December 07, 2017; Published: January 04, 2018

*Corresponding Address: Lawrence M Agius, Department of pathology, 27 "Ballarat” Guzeppe Caruana Street, TAL-Virtu, RABAT, RBT09 Malta, Europe and Formerly Mater Dei Hospital, TAL-QROQQ, University of Malta Medical School, MSIDA, Malta, Tel: 356-21451752;Email: lawrence.agius@um.edu.mt

How to cite this article: Lawrence M A. Permissive Changes in Consequential Carcinogenesis as Integral Deactivation of Pi3k Pathways, In Terms of the Single Oncogenic Transformation Step. Canc Therapy & Oncol Int J. 2018; 8(5): 555748. DOI: 10.19080/CTOIJ.2018.08.555748

Abstract

Active programs of interactivity allow for a permissiveness of cell systems within the range of specific and focal changes in oncogenesis. The incremental dimensions for further change call into operative consideration the dimensions for micro-environmental agonists that permeate systems of membrane and organelle and also participate in genetic instability. The revolutionary transfer of agents at the cell membrane incorporates ligand binding and stimulus/response within the further conditioning events of a plasma membrane that is modifiable by PI3K phosphorylinositol -3 kinase and phosphatases, Inclusion of parameters in oncogenesis are performance attributes of transfer dynamics leading to qualified re-definition of several cycles of change as portrayed integrally by a specific transformation event in carcinogenesis.

Introduction

Changes in normal cell metabolism, proliferation and motility of the affected cells allow for delineated events in evolutionary history of a given neoplasm. Several emerging novel therapies to improve the response to breast cancer hormone therapy are approved or are in development, such as inhibitors of CDK 4/6 and mTOR [1]. Calcium activated chloride channel A4 is a tumor suppressor and is involved in PI3K/AKT signaling and its downstream molecules promote bladder cancer cell proliferation [2]. Somatic or germ line mutations in the genes controlling PI3K processing appear related to receptor-bound status to the plasma membrane and include a widespread series of inhibitory events that may prove central to the inhibition of cancer growth. Silibiin suppresses bladder cancer through down regulation of the actin cytoskeleton and PI3K/Akt signaling pathways [3]. Performance dynamics further incorporate distribution of given chemical structures within site-specification of molecular functionality/dysfunctionality. Sarcoma gene mutations have included p53, RB, PI3K and IDH genes [4].

Subunits of PI3K

The regulatory p85 and the catalytic 110 isoforms that are induced by genetic or molecular experimental design may account for the possible therapeutic effects when manipulating the PI3K cascade pathways and may also induce such states as insulin- independent diabetes mellitus. Transforming growth factor is an early stage tumor suppressor and a late stage tumor oncogene and cross talks with Hippo, Wnt, EGFR/RAS and PI3K/AKT pathways; it is particularly implicated in cancer metastasis [5]. Signaling crosstalk is more prevalent in right colon carcinoma than left colon carcinoma and shows crosstalk with the RAS and P53 pathways [6].

In cases that further incorporate the viability issues of the cells, suppression of such PI3K cascades allow for a suppression of some aspects of carcinogenesis. Autophagy involves a central component in terms of class III phosphatidylinositol 3-kinase complex [7]. Indeed, dimensions of manipulation ofthe PI3K pathways have been considered accessible as anti-cancer targeting and should allow for widespread suppression of cancer genesis. Monoubiquitylation of KRAS at lysine 147 enhances Ras activation and promotes signaling through the RAF and PI3K pathways [8]. The incremental scope of PI3K suppression is further conformational change in receptor phosphorylation and includes the emergence of Akt activation- inhibition and of various intermediates in cellular signaling transduction.

The rather non-specific and widespread PI3K changes or mutations include amino-acid substitution and allow for anti-cancer approaches in therapeutic intervention. Inhibiting miR- 21 modulates biologic functions of gastric cancer cells via PTEN/ PI3K/mTOR pathway [9]. Metformin is associated with impaired cell proliferation in human endometrial carcinoma by suppressing PI3K/AKT/mTOR signaling [10]. The scope for further specification includes the consideration of interactions between p110alpha and p85 isoforms as context-reference in PI3K processing pathways.

Phosphatases

Phosphatases have been shown to abrogate the effects of changes in the suppression of PI3K pathways and appear to incorporate a relative if not entirely comprehensive anti-cancer modality measure in targeting cells undergoing carcinogenesis. In such measure, the progression of cancer establishment is dependent on suppression of p53 and Bcl2 actions and also creates various permissive steps that allow carcinogenesis to emerge as autonomous and also as response series of modalities in structure and function of PI3K pathways. Golgi membrane protein 1 shows oncogenic functions mainly through activation of the PI3K [AKT/ mTOR pathway and enhances prostate cancer cell proliferation, migration and invasion [11].

Increments of adjusted dimensions include growth factor receptivity and in real measure a series of receptor configurations that permissively incorporate the essential dynamics of metabolic turnover in carcinogenesis in terms of metabolic input and output of inhibitory or activating intermediates. PI3K/AKT pathway components play a critical role in carcinogenesis and resistance to anticancer drugs; the loss of PTEN and increased expression of p-AKT and p-mTOR in most gastric cancer cells are implicated in carcinogenesis [12].

Adaptor Proteins

The range of adaptor proteins, of rapamycin analogs, Akt and PTEN suppressor allows for a formulation that intensely incorporates a series of selective by-pathways in PI3K metabolism. Sufficient range dimensions allow tentative re-definitions of the widespread alterations as induced by PI3K isoforms and is indeed a complex reformulation in terms of variability of metabolic response beyond simple determinations of activated/suppressed consequence of the metabolic variability.

Interconnectivity and interaction lie at the center for propagation of such processes as cell proliferation, differentiation, motility and invasion within the further scope of a cellular milieu that characteristically is permissive and adaptable to the consequences of a manipulated series of PI3K pathways in carcinogenesis, Curcumin enhances the potent antitumor activity of nimustine hydrochloride against glioblastoma by suppressing the PI3K/AKT and NF-KappaB/COX-2 signaling pathways [13]. Angiogenesis is also a variable constant in carcinogenesis within the terms of ongoing permissive events that integrally conform to dimensions of a carcinogenesis that is paradoxically single event transformation and also a serial dimension in cellular biodiversity of the malignant transformation.

Modalities

Encompassed modality transformation steps are a variable spectrum for permissiveness in carcinogenesis that abrogates dimensions of stimulus/response on the one hand and progression of aberrant pathways as earmarked by the great diversity of oncogenesis that includes the promotion of growth and spread of tumor cells. Unbiased transcriptional and kinome reprogramming analyses are suggestive of increased c-Kit and PI3K/AKT pathway activation in resistant tumors and shed light on tumor-stroma dynamics with tissue plasticity in melanoma progression [14]. The dispersion dynamics include mutability as further reflected by systems of facilitation and suppression, as well-portrayed by phosphorylation and also non-typical phosphorylation processes.

The diversity issue is in keeping with a permissive micro-environment that transcends the instability of the genetic apparatuses in carcinogenesis. Included dimensional consequences of carcinogenesis are re-characterizations of the model PI3K pathways that serially change conformational indices of defined and redefined consequences of passenger genetic lesions or as indicated in some cases of virally induced oncogenesis. The FOXO3 and FOXM1 forehead box transcription factors function downstream to PI3K-Akt, Ras-ERK and JNK/p38MAPK signaling cascades and are central to cell proliferation, differentiation, cell survival, DNA damage repair and cell cycle control [15].

Permissivity

Proportionality is a poorly characterized phenomenon within the permissivity milieu of carcinogenesis and allows for incremental indices for the promotion of inhibitory adjustments in cell response, as for example projected by the systems of receptor- induced phosphorylation of kinase domains. The PI3K pathway has attracted immense interest as a therapeutic target in cancer [16]. Inclusion dynamics of permissiveness is best modeled in terms of consequential progression that adaptively conforms to dimensions of ongoing change and as well-denoted by the concept of cellular genetic instability. Zinc Finger Protein 703 enhances cell growth and metastasis through PI4K/Akt/GSK-3beta signaling in oral squamous cell carcinoma [17].

Lipid phosphorylation is relevant particularly with regard to membrane turnover dynamics and calls into question the concept of serial consequentiality as further promoted by genetic mutability and aberrant receptivity. Increments of carcinogenetic effect belie the dimensions of a specific transformation event that is initially and consequentially a serial promotion of such permissiveness. Incorporation of encompassed dynamics of permissiveness proceeds as aberrant response to carcinogenetic agents. FOXO transcription factors are negatively regulated by the PI3K-PKB/AKT signaling pathway and have been mainly considered to be tumor suppressors due to their inhibitory effect on cancer cell growth and survival [18]. Agonist actions are paramount events in terms of an inherent permissive milieu that arises within cells and propagates as micro-environmental conditioning and re-conditioning to aberrant signaling. MicroRNAs are closely related to lung cancer; miR- 1246 inhibits cell invasion and Epithelial Mesenchymal Transition process by targeting CXCR4 and blocking JAK/STAT and PI3K/ AKT signal pathways in lung cancer cells [19]. It is with specific referential conditioning of the cells that micro-environmental processes of progression assume a dominant determinant series of alterations in inducing cellular permissiveness.

Oncogenesis

Phosphate group participation in oncogenicity is relevant to a paradoxical activation of tyrosine kinases as well portrayed by the systems of incorporation of carcinogenesis. Indeed, the conceptual frameworks of permissiveness within such induced activation of oncogenesis belies the further incorporation of externally positioned agonist systems in the face of permissive dynamics of a single malignant transformation event.

Mutations in PIK3CA are very frequent in cancer and lead to sustained PI3K pathway activation; Pi3k signaling can contribute to the generation of irreversible genomic changes in cancer [20]. Re-conditioning is paramount consideration in the face of agonist action as simply conveyed by intra-cellular incorporation of a given and specific single agent transfer from the micro-environment. Transformation events are inherently accommodating systems that facilitate the incremental mimicry of evolutionary development of specific site events as well indicated by index steps that create novel alternatives in cellular receptor response in quasi-deficiency disorders. The HPV11E6 and HPV18E6 are important in initiating cellular transformation via deregulation of signaling pathways such as PI3KAKT and pathways in damage repair, cell survival, and cell proliferation [21]. Developmental consequences of deficient pathways portray the settings for aberrant insufficiency and also permissive adaptation to such site-specific focality of cellular response.

Conclusion

Dimensions of permissiveness that increases paradoxically in response/stimulus by an environmental agonist mechanism are paramount consideration in the evolutionary history of a carcinogenesis that is portrayed by the single transformation event in oncogenesis. Attributes beyond the given indices of cellular adaptive response belie the significant projections of integral cellular pathways that construe further evolution in terms especially of phosphorylation systems. Such phosphorylation further signifies the association of injury to stimulus/response in the manner of permissiveness and in the face of ongoing dynamics of induced transformation in malignancy. Perpetuating events further re-define the instance of malignant transformation within encompassed involvement of pathways that are well-exemplified by the PI3K metabolism.