Two signaling pathways are said to be important to regular human development i.e. the Wnt/Wingless (Wnt) and epidermal growth factor receptor (EGFR) pathways. They apparently interrelate in ways that could encourage tumor cell assault and metastasis. At least this is what a research from the University of Texas MD Anderson Cancer Center claims.
This recently characterized communication may include about three signaling components identified to associate with invasive cancer. They are activation of EGFR, elevated protein kinase CK2 activity, and augmented beta-catenin i.e. T-cell factor/lymphoid enhancer factor (TCF/LEF-1) transcriptional activity.
Senior author Zhimin Lu, MD, PhD, an associate professor in M. D. Anderson’s Department of Neuro-Oncology, commented, “These findings highlight the importance of Wnt-independent and non-canonical activation of beta-catenin in tumor development.”
Apparently, they also unlock new promises for biomarkers that could point out prognosis or guide treatment.
Cell signaling is claimed to be a complicated and specific procedure that could facilitate cells to develop, distinguish and eventually die. This methodical procedure is believed to be accountable for the standard growth of organs and tissues. Modifications in the signaling in cells and between cells, nonetheless, could disturb the cell-to-cell contact that may assist in keeping tumor cells in place. Loss of cell-to-cell contact could result in tumor cell relocation, attack and metastasis.
The Wnt signaling pathway supposedly plays a decisive function in cell growth, proliferation and separation. Mutations in this significant trail could result in the commencement of beta-catenin who is in charge for various kinds of cancer, counting colon cancer. Nevertheless, beta-catenin could also be triggered in a mutation-independent manner in other cancers.
A chief component of the Wnt pathway, beta-catenin supposedly merges with alpha-catenin and adjusts cell-cell adhesion. It apparently also communicates with alpha-catenin in the nucleus. The alpha-catenin constituent of this beta-catenin/alpha-catenin complex supposedly has an inhibitory outcome on beta-catenin that assists in keeping tumor cell migration and attack in check. This inhibition seems to be lost, nevertheless, when the EGFR pathway is generated. Upon start, beta-catenin could turn out to be untethered from alpha-catenin and translocates to the cell nucleus, where it supposedly augments expression of key target genes caught up in tumor cell invasion and metastasis.
The research team stumbled upon an astonishing finding. Beta-catenin also could pass through the nucleus by means of commencement of the EGFR pathway. The recently described pathway could disturb the beta-catenin/alpha catenin complex through an EGFR-extracellular receptor kinase (ERK)-protein kinase CK2- phosphorylation cascade. The scientists observed that this cascade could terminate in the phosphorylation of alpha-catenin and may eventually encourage the beta-catenin activation in the nucleus and following tumor cell invasion.
The scientists apparently discovered confirmation of the recently recognized pathway’s clinical relevance when they supposedly checked human glioblastoma specimens. Particularly, levels of alpha-catenin phosphorylation apparently associated with levels of ERK activity and with grades of tumor.
This research was published in Molecular Cell.