New! Sign up for our free email newsletter.
Science News
from research organizations

New regulatory axis revealed for the cancer relevant matrix metalloprotease MMP14

Date:
June 26, 2018
Source:
University of Helsinki
Summary:
Membrane-associated metalloprotease, MMP14, plays a significant role in different cancer tissues -- for instance in breast cancer and melanoma patients high MMP14 levels increase the risk to develop metastasis. The study revealed that Prox1 negatively regulates MMP14 protein levels by suppressing transcription of the MMP14 gene.
Share:
FULL STORY

Cancer and development are two different processes that surprisingly involve similar processes and regulatory circuits. With this premise, Silvia Gramolelli, a post-doctoral researcher in Professor Päivi Ojala´s group, University of Helsinki, uncovered a new regulatory axis for the membrane-associated metalloprotease, MMP14 (also named MT1-MMP).

When expressed on the surface of the cells, MMP14 eats up the extracellular matrix thus allowing the migration and invasion of the cells into the surrounding tissue. MMP14 participates in tissue remodelling during development and in physiological processes such as wound healing but it also plays a significant role in different cancer tissues, for instance in breast cancer and melanoma patients high MMP14 levels increase the risk to develop metastasis.

"The regulation of MMP14 levels is, thus, very important in both physiology and cancer and exploring how it is regulated is crucial for better understanding of these processes," Gramolelli states.

Gramolelli investigated whether Prox1, a transcription factor instrumental for lymphatic endothelial cell specification, development of several organs and in colorectal cancer stem cells, is suppressing MMP14.

"This hypothesis stemmed from the observation that in different cancers and healthy tissues with high MMP14 very low or no Prox1 was expressed," Professor Ojala explains.

Indeed, the study, published on June 22, 2018 in Scientific Reports, revealed that Prox1 negatively regulates MMP14 protein levels by suppressing transcription of the MMP14 gene. By manipulating Prox1 levels it was possible to modulate the amount of MMP14 in a plethora of systems and in a mouse model.

"The most surprising result was that by reintroducing Prox1 in highly invasive and metastatic breast cancer cells the ability of these cells to invade, the first step in metastasis formation, was inhibited," Dr. Gramolelli tells. She continues:

"This research for the first time links Prox1 to MMP14 in a regulatory axis that occurs and contributes to several physiological and pathological processes and could provide new leads to many aspects of biomedical research."


Story Source:

Materials provided by University of Helsinki. Note: Content may be edited for style and length.


Journal Reference:

  1. Silvia Gramolelli, Jianpin Cheng, Ines Martinez-Corral, Markus Vähä-Koskela, Endrit Elbasani, Elisa Kaivanto, Ville Rantanen, Krista Tuohinto, Sampsa Hautaniemi, Mark Bower, Caj Haglund, Kari Alitalo, Taija Mäkinen, Tatiana V. Petrova, Kaisa Lehti, Päivi M. Ojala. PROX1 is a transcriptional regulator of MMP14. Scientific Reports, 2018; 8 (1) DOI: 10.1038/s41598-018-27739-w

Cite This Page:

University of Helsinki. "New regulatory axis revealed for the cancer relevant matrix metalloprotease MMP14." ScienceDaily. ScienceDaily, 26 June 2018. <www.sciencedaily.com/releases/2018/06/180626113359.htm>.
University of Helsinki. (2018, June 26). New regulatory axis revealed for the cancer relevant matrix metalloprotease MMP14. ScienceDaily. Retrieved March 28, 2024 from www.sciencedaily.com/releases/2018/06/180626113359.htm
University of Helsinki. "New regulatory axis revealed for the cancer relevant matrix metalloprotease MMP14." ScienceDaily. www.sciencedaily.com/releases/2018/06/180626113359.htm (accessed March 28, 2024).

Explore More

from ScienceDaily

RELATED STORIES