Low-order assemblies drive oncogenic RTK fusion signalling without condensation.

Low-order multimerization of cytoplasmic RTK fusions drives strong Ras-Erk signalling and transformation without mesoscale condensation, including for EML4-ALK where signalling poorly correlates with condensates.

• Why it matters: It remains unclear how cytoplasmic RTK fusions activate plasma-membrane-origin downstream pathways, and whether condensates are required or whether smaller diffuse assemblies suffice.
• What they did: Using advanced microscopy, single-cell analysis, and synthetic fusions, the study tested EML4-ALK and engineered ALK/RET constructs, including cytoplasmic dimers and constitutively active monomers, for Ras-Erk signalling and tumour phenotypes.
• The result: Cytoplasmic dimers of ALK or RET domains—and even constitutively active monomers—induced strong Ras-Erk signalling without condensates, and non-condensing fusions transformed cells in vitro and in subcutaneous tumour models; across diverse fusions, condensation was rare and not linked to signalling.

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