A mechanism that restores adhesion in cancer cells

December 6, 2017

Cell boundary surface tension by actomysin contraction induces the mechanism

Collaborative intra-RIKEN research between the Center for Developmental Biology and CSRS has discovered a mechanism that restores intercellular adhesion in colon cancer–derived cell lines.

Normal epithelial cell tissue is polar, which allows it to firmly adhere to apical cell regions and to thus maintain tissue stability. In cases of cancer, this polarity is lost as the cancer progresses, which disturbs intercellular adhesion structure. Various adhesion abnormalities are observed in cancer cell lines, which may increase their ability to invade as well as their metastatic potential. Currently, no treatment can reverse these types of adhesion abnormalities.

Using colon cancer–derived cancer cells that fail to adhere, researchers searched among 160,000 compounds for potential drugs that could restore adhesion. They discovered several inhibitors that could accomplish this by breaking down microtubulepolymerization in the cytoskeleton.

By blocking microtubule polymerization, the inhibitors and similar drugs activate the intracellular signal protein RhoA, which causes actomyosin—a complex of actin and myosin on the cell surface—to contract. This contraction is transmitted as "tension" between cells and attracts another actin regulatory protein. The result is the return of a nearly normal adhesive structure to the colon-cancer cells.

Researchers believe that finding additional adhesion-restoring agents and confirming that they, and the currently discovered compounds, affect cancer cells the same way in vivo will lead to the development of new cancer-treatment methods.

 

Original article
Nature Communications doi:10.1038/s41467-017-01945-y
S. Ito, S. Okuda, M. Abe, M. Fujimoto, T. Onuki, T. Nishimura, M. Takeichi,
"Induced cortical tension restores functional junctions in adhesion-defective carcinoma cells".

Contact
Tetsuo Onuki
Deputy Unit Leader
Seed Compounds Exploratory Unit for Drug Discovery Platform