Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

05 Mar 2017 - 09 Mar 2017
20 Mar 2017 - 23 Mar 2017
12 Apr 2017 - 14 Apr 2017

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

By BiotechDaily International staff writers
Posted on 09 Jul 2013
ADVERTISEMENT
SARTORIUS AG
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




Channels

Drug Discovery

view channel
Image: The experimental drug NGI-1 slows cancer growth by blocking glycosylation of the epidermal growth factor receptor (EGFR), which is shown in the above diagram (Photo courtesy of Wikimedia Commons).

Experimental Drug Slows Lung Cancer Growth by Blocking Protein Glycosylation

An interesting new experimental anti-cancer drug slows growth of certain lung tumor cells by preventing the glycosylation of critical cell surface receptor proteins. Asparagine (N)-linked glycosylation... Read more

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Business

view channel

Collaborative Agreement to Aid in Setting Guidelines for Evaluating Potential Ebola Therapy

Cooperation between an Israeli biopharmaceutical company and medical branches of the US government is designed to set ground rules for continued evaluation of an experimental therapy for Ebola virus disease. RedHill Biopharma Ltd. (Tel Aviv, Israel), a biopharmaceutical company primarily focused on development and c... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.