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.

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Select Langenau Lab Publications in Rhabdomyosarcoma

  • MYOD1 mutation drives cancer stem cell pathways and therapy-resistance in spindle cell/sclerosing rhabdomyosarcoma. Wei Y, Corchete Sánchez LA, Mathavarajah S, Antelo D, Wang S, Lee J, Weissman AD, Kannambadi DD, Qin Q, Danielli SG, Quantin EJ, Eng TC, Veloso A, Wang Y, Neilsen GP, Yan C, Yang VS, Patel AG, Koo SC, Odeniyide P, Pratilas CA, Rivera MN, Rheinbay E, Langenau DM. Nat Commun. 2026 Jun 3. PubMed

  • The PIK3CA/AKT pathway drives therapy resistance in rhabdomyosarcoma. Yang Q, Wang Y, Corchete Sanchez LA, Mathavarajah S, Qin Q, Wei Y, Alpert E, Whelton L, Sharma P, Strom S, Oultache I, Iafrate AJ, Pinello L, Rheinbay E, Yan C, Langenau DM. Nat Commun. 2025 Dec 10;17(1):65. PubMed

  • Single cell transcriptomic profiling identifies tumor-acquired and therapy-resistant cell states in pediatric rhabdomyosarcoma. Danielli SG, Wei Y, Dyer MA, Stewart E, Sheppard H, Wachtel M, Schäfer BW, Patel AG, Langenau DM. Nat Commun. 2024 Jul 26;15(1):6307. PubMed

  • Single-cell analysis and functional characterization uncover the stem cell hierarchies and developmental origins of rhabdomyosarcoma. Wei Y, Qin Q, Yan C, Hayes MN, Garcia SP, Xi H, Do D, Jin AH, Eng TC, McCarthy KM, Adhikari A, Onozato ML, Spentzos D, Neilsen GP, Iafrate AJ, Wexler LH, Pyle AD, Suvà ML, Dela Cruz F, Pinello L, Langenau DM. Nat Cancer. 2022 Aug;3(8):961-975. PubMed

  • 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:e37202. PubMed

  • 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

  • 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

For a full list of Langenau Lab publications, find out more here.