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<p>Triple-negative breast cancer (TNBC) is a very aggressive form of breast cancer and Black American (BA) women face disproportionately higher mortality rates than White American (WA) women. The molecular mechanism behind this disparate clinical outcome remains poorly understood. We find that BA TNBC patients exhibit higher protein expression of KRT17 compared to WA TNBC and non-TNBC patients and correlates to poor distant metastasis-free survival. Mechanistic studies in metastatic mouse TNBC tumors with higher Krt17 demonstrates higher Wnt signaling targets, cancer stem cells (CSCs), which positively correlates to several metastasis signatures, supporting clinical data. Consistently, KRT17<sup>high</sup> BA patient tumors display higher activated Wnt signaling. Furthermore, Krt17 regulates Wnt signaling to drive recruitment of γδ T-cells in both mouse and human samples, which can be reversed by targeting Wnt signaling, identifying the Krt17-Wnt signaling axis as a critical driver of clinical disparities and a novel targetable vulnerability for BA TNBC patients.</p>

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KRT17 promotes triple negative breast cancer through activation of Wnt signaling and γδ T-cells recruitment

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月26日

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  • Chermakani Panneer Selvam,
  • Gatha Thacker,
  • Ukjin Kim,
  • Youley Tjendra,
  • Melinda M. Boone,
  • Samantha Henry,
  • Camila O. Dos Santos,
  • Rumela Chakrabarti

摘要

Triple-negative breast cancer (TNBC) is a very aggressive form of breast cancer and Black American (BA) women face disproportionately higher mortality rates than White American (WA) women. The molecular mechanism behind this disparate clinical outcome remains poorly understood. We find that BA TNBC patients exhibit higher protein expression of KRT17 compared to WA TNBC and non-TNBC patients and correlates to poor distant metastasis-free survival. Mechanistic studies in metastatic mouse TNBC tumors with higher Krt17 demonstrates higher Wnt signaling targets, cancer stem cells (CSCs), which positively correlates to several metastasis signatures, supporting clinical data. Consistently, KRT17high BA patient tumors display higher activated Wnt signaling. Furthermore, Krt17 regulates Wnt signaling to drive recruitment of γδ T-cells in both mouse and human samples, which can be reversed by targeting Wnt signaling, identifying the Krt17-Wnt signaling axis as a critical driver of clinical disparities and a novel targetable vulnerability for BA TNBC patients.