Self-Renewal Programs in Rhabdomyosarcoma
Rhabdomyosarcoma is a common muscle sarcoma of childhood and can be modeled using transgenic zebrafish. Using fluorescent transgenic zebrafish to label functionally distinct tumor cells, our group has identified self-renewing cancer stem cells that drive continued tumor growth at relapse. Importantly, these same cell types can be identified in human muscle cancers and share similar pathways to drive cancer growth. Building on the dynamic live cell imaging approaches available in the zebrafish ERMS model, our laboratory has uncovered a number of molecular pathways that drive continued tumor growth and progression by regulating cancer stem cell function including RAS, NOTCH1, MYOD/MYF5, WNT/Beta-catenin, and VANGL2.
Select Langenau Lab Publications in Rhabdomyosarcoma
tp53 deficiency causes a wide tumor spectrum and increases embryonal rhabdomyosarcoma metastasis in zebrafish. Ignatius MS, Hayes MN, Moore FE, Tang Q, Garcia SP, Blackburn PR, Baxi K, Wang L, Jin A, Ramakrishnan A, Reeder S, Chen Y, Nielsen GP, Chen EY, Hasserjian RP, Tirode F, Ekker SC, Langenau DM. Elife. 2018; 7. pii: e37202. PubMed | PDF
Vangl2/RhoA Signaling Pathway Regulates Stem Cell Self-Renewal Programs and Growth in Rhabdomyosarcoma. Hayes MN, McCarthy K, Jin A, Oliveira ML, Iyer S, Garcia SP, Sindiri S, Gryder B, Motala Z, Nielsen GP, Borg JP, van de Rijn M, Malkin D, Khan J, Ignatius MS, Langenau DM. Cell Stem Cell. 2018; 22(3):414-427. PubMed | PDF
The NOTCH1/SNAIL1/MEF2C Pathway Regulates Growth and Self-Renewal in Embryonal Rhabdomyosarcoma. Ignatius MS, Hayes MN, Lobbardi R, Chen EY, McCarthy KM, Sreenivas P, Motala Z, Durbin AD, Molodtsov A, Reeder S, Jin A, Sindiri S, Beleyea BC, Bhere D, Alexander MS, Shah K, Keller C, Linardic CM, Nielsen PG, Malkin D, Khan J, Langenau DM. Cell Reports. 2017; 19(11):2304-2318. PubMed | PDF
Myogenic regulatory transcription factors regulate growth in rhabdomyosarcoma. Tenente IM, Hayes MN, Ignatius MS, McCarthy K, Yohe M, Sindiri S, Gryder B, Oliveira ML, Ramakrishnan A, Tang Q, Chen EY, Petur Nielsen G, Khan J, Langenau DM. Elife. 2017; 6. pii: e19214. PubMed | PDF
In vivo imaging of tumor-propagating cells, regional tumor heterogeneity and dynamic cell movements in embryonal rhabdomyosarcoma. Ignatius MS, Chen E, Elpek NE, Fuller A, Tenente IM, Clagg R, Liu S, Blackburn JS, Linardic CM, Rosenberg A, Nielsen PG, Mempel TR, Langenau DM. Cancer Cell. 2012; 21(5):680-93. PubMed | PDF
For a full list of Langenau Lab publications, find out more here.