The cnidarian origin of the proto-oncogenes NF-κB/STAT and WNT-like oncogenic pathway drives the ctenophores (Review)

Abstract

The cell survival pathways of the diploblastic early multicellular eukaryotic hosts contain and operate the molecular machinery resembling those of malignantly transformed individual cells of highly advanced multicellular hosts (including Homo). In the present review, the STAT/NF-κB pathway of the cnidarian Nematostella vectensis is compared with that of human tumors (malignant lymphomas, including Reed-Sternberg cells) pointing out similarities, including possible viral initiation in both cases. In the ctenophore genome and proteome, β-catenin gains intranuclear advantages due to a physiologically weak destructive complex in the cytoplasm, and lack of natural inhibitors (the Dickkopfs). Thus, a scenario similar to what tumor cells initiate and achieve is presented through several constitutive loss-of-function type mutations in the destructive complex and in the elimination of inhibitors. Vice versa, malignantly transformed individual cells of advanced multicellular hosts assume pheno-genotypic resemblance to cells of unicellular or early multicellular hosts, and presumably to their ancient predecessors, by returning to the semblance of immortality and to the resumption of the state of high degree of resistance to physicochemical insults. Human leukemogenic and oncogenic pathways are presented for comparisons. The supreme bioengineers RNA/DNA complex encoded both the malignantly transformed immortal cell and the human cerebral cortex. The former generates molecules for the immortality of cellular life in the Universe. The latter invents the inhibitors of the process in order to gain control over it.

Valproic acid attenuates traumatic spinal cord injury-induced inflammation via STAT1 and NF-κB pathway dependent of HDAC3

“…The STAT1 pathway plays a critical role in mediating the NF-kB p65 nuclear translocation [ 13 , 14 ]. The lysine acetylation of the STAT1 seemed to be dispensable for the NF-kB releasing from its inhibitor IκB inhibition in response to damage stimuli [ 14 ].…”

“…The activation of the NF-κB is initiated by IκB kinase (IKK), which degrades cytoplasmic IκB protein, which triggers the rapid release of NF-κB from IκB and intranuclear translocation [ 11 , 12 ]. The activation process co-exists with signal transducers and activators of transcriptions (STATs) [ 13 , 14 ]. The DNA-binding STATs enter from the cytoplasm to the nucleus and activate their target genes at chromosome 19q13.…”

“…These genes include B cell lymphoma (Bcl)-3, which encodes elements of IκB from the NF-κB pathway [ 15 – 17 ]. Releases of the NF-κB proteins for intranuclear transfer allow them to bind to their target gene promoters that encode chemokines and cytokines, including persistently activated STATs [ 13 , 16 , 17 ].…”

Phylogenetic evidence for the modular evolution of metazoan signalling pathways

“…STAT-like transcription factors have been reported from all major lineages of unikonts; however, most of these molecules lack the C-terminal transactivation (TAD) domain. Despite this, the cnidarian STAT-like protein appears to complex with nuclear factor kappa-B (NFkB) to serve as part of the rudimentary immune system [140]. This suggests that STAT-like proteins may have engaged in transcriptional regulation before becoming associated with the JAK signalling cascade.…”

Treatment with β-elemene combined with paclitaxel inhibits growth, migration, and invasion and induces apoptosis of ovarian cancer cells by activation of STAT-NF-κB pathway

“…NF-kB signaling pathway may be a promising therapeutic target for treating malignant ovarian cancers (27). Additionally, the STAT/NF-kB signal pathway is involved in human tumors and fulfills essential pathological features by allowing to translocate from the cytoplasm into the nucleus for the activation of oncoprotein promoter DNAs (28). In this study, we investigated the combined anticancer effect of b-elemene and paclitaxel on ovarian cancer and explored the association between b-elemene +paclitaxel and STAT3-NF-kB signal pathway in SKOV3 cells.…”