Abstract
Ectodermal neural cortex 1 (ENC1) is an actin-binding protein and has been known to be upregulated in several cancers, but the molecular mechanisms through which it contributes to the pathology of CRC have largely been elusive. We utilized data mining and validated the aberrant expression of ENC1, following which phenotypic traits of malignancy were assessed in vitro. Ruxolitinib was used as a surrogate to compare the effects of ENC1 expression and silencing on the JAK-STAT-AKT pathway. In vivo models were employed to confirm the in vitro observations. Computation analysis, strengthened by in situ and in vitro data, confirmed the overexpression of ENC1 in CRC and predicted a poor prognosis, while enhanced cell proliferation, invasion, migration, EMT, and stemness were associated with ENC1 overexpression. Silencing of ENC1 downregulated the phenotypes. Additionally, silencing of ENC1 significantly reduced the activation of JAK2 and consequent activation of STAT5 and AKT comparable to ruxolitinib inhibition of JAK2. Silencing of ENC1 resulted in lesser tumor volumes and fewer numbers of tumors, in vivo. These data suggest that ENC1 induces CRC through the JAK2-STAT5-AKT axis. ENC1 is a suitable diagnostic marker for CRC detection, and ENC1 targeting therapies may suppress CRC progression.
Highlights
A recently concluded longitudinal study undertaken in 195 countries over a period of 27 years (1990–2017) is an in-depth analysis of incidence, mortality, disability, and associated risk factors in Colorectal Cancer Collaborators (CRC) (2019)
In the current study using a combinatorial approach of in vitro and in vivo models, we report that Ectodermal neural cortex 1 (ENC1) expression in CRC is associated with increased cellular proliferation, migration, invasion, and tumor growth, and this was likely mediated through the JAK2-STAT5-AKT axis
We found that the phosphorylation levels of JAK2, STAT5, and AKT increased in ENC1-overexpressed CRC cells (Figure 5C) but decreased in ENC1-silenced CRC cells (Figure 5D)
Summary
A recently concluded longitudinal study undertaken in 195 countries over a period of 27 years (1990–2017) is an in-depth analysis of incidence, mortality, disability, and associated risk factors in Colorectal Cancer Collaborators (CRC) (2019). During the period of the study, there was a consistent increase in the age-standardized incidence rate, and the ENC1 Facilitates Colorectal Carcinoma via JAK2/STAT5/AKT Axis findings are concurrent with the recent GLOBOCAN database, estimating about 1,800,977 incident cases and a million deaths due to CRC (Bray et al, 2018). These figures are attributed to higher CRC screening and are indicative of a decline or stabilization. The cross talk between these pathways in CRC progression has been discussed (Koveitypour et al, 2019)
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