Features | Partner Sites | Information | LinkXpress
Sign In
JIB
GLOBETECH PUBLISHING
GLOBETECH PUBLISHING

Signaling Regulatory Protein Found That Mediates Metastasis of Human Colorectal Cancer Cells

By BiotechDaily International staff writers
Posted on 09 Jul 2013
The direct effect of the signaling regulatory protein km23-1 (also called DYNLRB1/mLC7-1/robl-1/Dnlc2a/DYRB1) on TGF-beta (transforming growth factor beta) defines its role in mediating the migration, invasion, and tumor growth of human colorectal carcinoma (CRC) cells.

TGF-beta acts as an antiproliferative factor in normal epithelial cells and at early stages of cancer development. However, when a cell is transformed into a cancer cell, parts of the TGF-beta signaling pathway are mutated, and TGF-beta no longer controls the cell. These cancer cells and surrounding stromal cells (fibroblasts) begin to proliferate. Both types of cell increase their production of TGF-beta. This TGF-beta acts on the surrounding stromal cells, immune cells, endothelial, and smooth muscle cells causing immunosuppression and angiogenesis, which makes the cancer more invasive.

Investigators at the Pennsylvania State College of Medicine (Hershey, USA) had previously described km23-1 as a novel modulator of the actin cytoskeleton that also regulated the Ras oncogene and mitogen-activated protein kinase activities in TGF-beta-sensitive epithelial cells.

In a new study, the investigators examined the functional role of this signaling regulatory protein in mediating the migration, invasion, and tumor growth of human CRC cells. Towards this end, they used small interfering RNA (siRNA) to deplete levels of km23-1 in cultures of human CRC cells.

They reported in the June 3, 2013, online edition of the journal PLOS ONE that depletion of km23-1 inhibited constitutive extracellular signal-regulated kinase (ERK) activation, as well as proinvasive ERK effector functions that included TGF-beta promoter transactivation, and TGF-beta secretion. In addition, knockdown of km23-1 reduced the paracrine effects of CRC cell-secreted factors in conditioned medium and in fibroblast co-cultures. Furthermore, km23-1 depletion in human CRC cells reduced cell migration and invasion, as well as expression of the ERK-regulated, metastasis-associated scaffold protein Ezrin. Km23-1 inhibition significantly suppressed tumor formation in an in vivo model system.

"The type of cell movement, or migration, has important implications with respect to the detection of tumor cells in the blood of cancer patients, as well as for the development of new treatments," said senior author Dr. Kathleen M. Mulder, professor of biochemistry and molecular biology at Pennsylvania State College of Medicine. "Km23-1 may be able to help in this process due to its role in the assembly of large groups of proteins favorable to cancer invasion. If we can block km23-1, we can stop the spread of colon cancer earlier, but we would also affect other important functions of the protein. In order to address this issue, we are now trying to find the specific partners of km23-1 that contribute to the invasion of the cancer cells. Then we can design more precise therapeutic agents that target critical regions of km23-1 rather than eliminating the entire protein."

Related Links:

Pennsylvania State College of Medicine




comments powered by Disqus

Channels

Drug Discovery

view channel
Image: Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells (Photo courtesy of the University of Texas, Austin).

Experimental Drug Kills Cancer Cells by Interfering with Their Ion Transport Mechanism

An experimental anticancer drug induces cells to enter a molecular pathway leading to apoptosis by skewing their ion transport systems to greatly favor the influx of chloride anions. To promote development... Read more

Therapeutics

view channel
Image: Liver cells regenerated in mice treated with a new drug (right) compared with a control group (center) after partial liver removal. Healthy liver cells are shown at left (Photo courtesy of Marshall et al, 2014, the Journal of Experimental Medicine).

New Drug Triggers Liver Regeneration After Surgery

Investigators have revealed that an innovative complement inhibitor decreases complement-mediated liver cell death, and actually stimulates postsurgery liver regrowth in mice. Liver cancer often results... Read more

Lab Technologies

view channel

White-Matter Deficits Found in Codeine-Containing Cough Syrup Users

A magnetic resonance imaging (MRI) study of chronic users of codeine-containing cough syrups (CCS) has found deficits in specific regions of brain white matter and linked these changes with increased impulsivity in codeine-containing cough syrup users. These findings were consistent with findings from earlier research of... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.