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Increased prevalence of hybrid epithelial/mesenchymal state and enhanced phenotypic heterogeneity in basal breast cancer.
Sahoo, Sarthak; Ramu, Soundharya; Nair, Madhumathy G; Pillai, Maalavika; San Juan, Beatriz P; Milioli, Heloisa Zaccaron; Mandal, Susmita; Naidu, Chandrakala M; Mavatkar, Apoorva D; Subramaniam, Harini; Neogi, Arpita G; Chaffer, Christine L; Prabhu, Jyothi S; Somarelli, Jason A; Jolly, Mohit Kumar.
Afiliación
  • Sahoo S; Department of Bioengineering, Indian Institute of Science, Bangalore 560012, India.
  • Ramu S; Department of Bioengineering, Indian Institute of Science, Bangalore 560012, India.
  • Nair MG; Division of Molecular Medicine, St. John's Research Institute, St. John's Medical College, Bangalore 560012, India.
  • Pillai M; Department of Bioengineering, Indian Institute of Science, Bangalore 560012, India.
  • San Juan BP; Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
  • Milioli HZ; Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
  • Mandal S; Department of Bioengineering, Indian Institute of Science, Bangalore 560012, India.
  • Naidu CM; Division of Molecular Medicine, St. John's Research Institute, St. John's Medical College, Bangalore 560012, India.
  • Mavatkar AD; Division of Molecular Medicine, St. John's Research Institute, St. John's Medical College, Bangalore 560012, India.
  • Subramaniam H; Department of Bioengineering, Indian Institute of Science, Bangalore 560012, India.
  • Neogi AG; Department of Bioengineering, Indian Institute of Science, Bangalore 560012, India.
  • Chaffer CL; Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
  • Prabhu JS; University of New South Wales, UNSW Medicine, Sydney, NSW 2010, Australia.
  • Somarelli JA; Division of Molecular Medicine, St. John's Research Institute, St. John's Medical College, Bangalore 560012, India.
  • Jolly MK; Department of Medicine, Duke University, Durham, NC 27708, USA.
iScience ; 27(7): 110116, 2024 Jul 19.
Article en En | MEDLINE | ID: mdl-38974967
ABSTRACT
Intra-tumoral phenotypic heterogeneity promotes tumor relapse and therapeutic resistance and remains an unsolved clinical challenge. Decoding the interconnections among different biological axes of plasticity is crucial to understand the molecular origins of phenotypic heterogeneity. Here, we use multi-modal transcriptomic data-bulk, single-cell, and spatial transcriptomics-from breast cancer cell lines and primary tumor samples, to identify associations between epithelial-mesenchymal transition (EMT) and luminal-basal plasticity-two key processes that enable heterogeneity. We show that luminal breast cancer strongly associates with an epithelial cell state, but basal breast cancer is associated with hybrid epithelial/mesenchymal phenotype(s) and higher phenotypic heterogeneity. Mathematical modeling of core underlying gene regulatory networks representative of the crosstalk between the luminal-basal and epithelial-mesenchymal axes elucidate mechanistic underpinnings of the observed associations from transcriptomic data. Our systems-based approach integrating multi-modal data analysis with mechanism-based modeling offers a predictive framework to characterize intra-tumor heterogeneity and identify interventions to restrict it.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2024 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos