MAY 07, 2020 3:40 PM PDT

Yet Another Cancer Linked Tyrosine Kinase

WRITTEN BY: Jasper Cantrell

In a cell, there are tens of thousands of individual components. Each component has a specific activity that the cell needs to function and survive. Controlling this chaos is the role of signaling pathways. Researchers realized this decades ago and began to investigate how these complex systems worked. A common factor for many of them is their origin of activation. Many of these pathways begin with the activation of receptors situated on the outside the cell. These receptors interact with extracellular signals from the environment and relay the signal into the cell.

Many diseases hijack these receptors, turning them on or off and eliciting an abnormal response by the cell. Cancer is a prime example, with many tumor-promoting activities being traced back to abnormal receptor activities. One such receptor is called discoidin domain receptor 1 (DDR1), a relatively new receptor with a signaling pathway that is not well known just yet. A group from Spain investigated DDR1’s role in promoting metastasis and cell invasion.

DDR1 is a receptor that binds collagen type 1. It was observed that many invasive cancers exhibit an increase in the expression levels of DDR1. This observation led to the hypothesis that DDR1 may be linked to these activities. The group conducted a set of in vitro experiments to examine this link further.

The experiments in question were quite straightforward, with the intent to explore the possible mechanisms behind DDR1’s pro-metastatic activities. Using three cancer cell lines, a colon, skin, and hepatocellular line, they created tested the levels of DDR1.  All three cancers expressed DDR1 at a higher level than healthy cells. They then inhibited DDR1 using both a chemical inhibitor and a small interfering RNA (siRNA) targeted at DDR1. They then followed the effects and observed a significant decrease in the phosphorylation of mitogen-activated protein kinase (ERK) and protein kinase B (Akt) as well as the reduction of matric metallopeptidase 9 (MMP9). They also observed a significant collagen type 1 production from all cancer cell lines, inferring a positive feedback loop might be involved.

ERK and Akt are tyrosine kinases responsible for signaling pathways involved in cellular proliferation, while MMP9 is linked to cell adhesion. ERK and Akt are often abnormally activated in cancer, so DDR1 overexpression is likely to turn on these pathways and produce a similar effect. Following up on the MMP9 observation, the group also found that inhibition of DDR1 in the cell lines tested impaired cell adhesion onto a collagen type 1 film. Cell adhesion is an essential event in cancer invasion, so this may explain why DDR1 overexpression is seen in invasive cancers.

The signaling pathways surrounding cancer are often interconnected and quite complex. Many potential anti-cancer drugs target one or more of these pathways and cause abnormal effects as it creates a cascade reaction across several pathways. While a relatively quick foray into DDR1’s tumor-promoting activities, the examination of yet another signaling pathway connected to cancer is a win. The group leaves room for further investigation and even alludes to work in progress that may elaborate more on these findings.

Sources: Cell Adhesion and Migration, HeyNowScience
 

About the Author
  • Hey everyone! My name is Jasper and, considering I am pretty new here to Labroots, I figured I would introduce myself. I received my bachelor’s from the University of California at Riverside back in 2016. I started off my career a few years ago with a job at a University over in New York, before moving over into the industry. I'm happy to be writing content for Labroots, and I hope you enjoy it!
You May Also Like
MAR 24, 2020
Clinical & Molecular DX
MAR 24, 2020
Ultra sensitive cancer diagnostic detects DNA "fingerprints" in liquid biopsies
  Researchers from the Broad and Dana-Farber Cancer Institutes have developed a diagnostic technology that can moni ...
APR 04, 2020
Cancer
APR 04, 2020
Unique Cancer Mutation Hijacks Nearby Signaling Pathway
  In cancer, tyrosine kinase mutations are quite common. MET is one such example that normally binds its native lig ...
APR 14, 2020
Genetics & Genomics
APR 14, 2020
How Deer Antlers Can Teach Us About Cancer Treatment
Deer antlers grow faster than cancerous tumors.
APR 21, 2020
Cancer
APR 21, 2020
Scientists develop tumor immunity map
A new study published in eLife describes the findings from a study that has successfully mapped tumor cell molecule ...
MAY 02, 2020
Drug Discovery & Development
MAY 02, 2020
Glioblastoma Treatment Using Schizophrenic Drug Plus Radiation
A therapeutic used for the treatment of schizophrenia could be a gateway for targeting glioblastoma, one of the deadlies ...
MAY 19, 2020
Cancer
MAY 19, 2020
Great ape genomes closer to human tumors than human genomes
A new study analyzing cancer from an evolutionary perspective reports that the distribution of mutations in human tumors ...
Loading Comments...