A novel mechanism underlying Rhabdomyosarcoma, a type of childhood cancer of the soft tissue

11 Mar 2018

A novel mechanism underlying Rhabdomyosarcoma, a type of childhood cancer of the soft tissue


By Dr. Sam Mathew, Intermediate Fellow

Regional Centre for Biotechnology (RCB), Faridabad

Recent research from our group identifies role of a protein that regulates the function of MET, a cancer-causing gene, in the development of cancer affecting the skeletal soft tissue. Insights from this study might help develop better cancer treatment strategies for deadly childhood cancers of the muscle such as Rhabdomyosarcoma.

Rhabdomyosarcoma is a cancer which occurs mostly in children, accounting for about 3% of all childhood cancers. Rhabdomyosarcoma generally develops in the muscles around the bone that are responsible for movement and slowly spreads to other parts of the body. Rhabdomyosarcoma tumor cells exhibit several similarities to developing muscle cells, including expression of muscle differentiation proteins such as MyoD, Myogenin and myosin heavy chains. However, rhabdomyosarcoma tumor cells have two key differences compared to normal muscle cells: first, unlike developing muscle cells, the tumor cells do not stop dividing and second, unlike muscle cells, the tumor cells do not become specialized to perform contractile function.

MET is a cancer-causing gene (oncogene) mutated and mis-regulated in numerous types of cancers. MET encodes for a receptor protein in a cell called the tyrosine kinase protein, a class of proteins which mediate signals crucial for cellular processes such as survival, movement, division and shape changes. Signaling mediated by MET is required during mammalian muscle development, for the migration of cells that give rise to the muscle, into target organs such as limbs, and tongue.

Recent work from our laboratory identifies SPRY2, a protein which is known to modulate signaling through receptor tyrosine kinases, as a crucial MET regulator.  We found that MET and SPRY2 proteins interact with each other in rhabdomyosarcoma cells. This interaction is crucial because loss of SPRY2 function leads to a significant reduction in MET protein levels, indicating that SPRY2 is essential for MET protein stability in rhabdomyosarcoma. This provides a new mechanism by which MET levels are mis-regulated in rhabdomyosarcoma. Notably, loss of SPRY2 or MET resulted in decreased migratory capability in the tumor cells, indicating that these proteins and their interaction is vital to tumor invasive properties. We also find that both MET and SPRY2 are important for rhabdomyosarcoma cell survival and cell division, thus identifying a novel therapeutic intervention point in rhabdomyosarcoma.


SPRY2 is a novel MET regulator that regulates metastatic potential and differentiation in rhabdomyosarcoma. Saini, M., A. Verma, and S.J. Mathew. Cell Death and Disease. February 2018. 


Banner image: Flurescent microscopy image of embryonal rhabdomyosarcoma cells labeled for SPRY2 (red), MET (green) and DAPI (blue), showing that SPRY2 co-localizes with MET. Credit: Dr. Sam Mathew