Related Experiment Video

Updated: May 15, 2026

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics
08:11

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics

Published on: March 26, 2018

Cancer-linked ANKRD26-RET uses an unusual combination of pathomechanisms leading to strongly increased cell

Anna S Englisch1, Sarah A Hofbrucker-MacKenzie1, Klara Metzner1

  • 1Institute of Biochemistry I, Jena University Hospital, Friedrich Schiller University Jena, 07743 Jena, Germany.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|May 13, 2026
PubMed

Insights

Papillary thyroid carcinoma involves ANKRD26-RET fusions that promote cancer by anchoring to the membrane and self-associating. Targeting ANKRD26 dysfunction alongside RET kinase activity may improve therapeutic outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Papillary thyroid carcinoma (PTC) is associated with ANKRD26-RET fusions, but their pathomechanisms are not fully understood.
  • RET fusions typically involve loss of membrane association; however, ANKRD26-RET exhibits increased plasma membrane anchoring.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying the pathomechanisms of the ANKRD26-RET fusion.
  • To investigate the role of ANKRD26 in RET signaling and its contribution to PTC.

Main Methods:

  • Investigated the ANKRD26(1-1405)-RET(713-1114) fusion protein.
  • Analyzed ANKRD26-mediated membrane association and self-association.
  • Assessed RET phosphorylation, cell proliferation, and colony formation.
  • Evaluated the efficacy of RET inhibitors (RXDX-105/agerafenib and BLU-667/pralsetinib).

Main Results:

  • ANKRD26-RET promotes aberrant RET signaling through plasma membrane anchoring and self-association.
  • This leads to constitutive RET phosphorylation (Y905, Y981, Y1015, Y1062), increased cell proliferation, and colony formation.
  • While RET inhibitors suppressed colony formation, they only moderately affected cell proliferation, suggesting ANKRD26 dysfunction also contributes.

Conclusions:

  • The ANKRD26-RET fusion drives PTC through a unique mechanism involving membrane association and self-association, distinct from other RET fusions.
  • Therapeutic strategies may need to target both RET kinase activity and ANKRD26 dysfunction for effective PTC treatment.
Keywords:
ANKRD26-RET-intrinsic pathomechanismsCancerInhibitors agerafenib and pralsetinibN-Ank proteinsPlasma membrane associationRET kinase autophosphorylationSelf-association

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