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

Panneer Selvam, Chermakani, Thacker, Gatha, Kim, Ukjin, Tjendra, Youley, Boone, Melinda M, Henry, Samantha, Dos Santos, Camila O, Chakrabarti, Rumela (March 2026) KRT17 promotes triple negative breast cancer through activation of Wnt signaling and γδ T-cells recruitment. Communications Biology. ISSN 2399-3642

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Abstract

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.

Item Type: Paper
Subjects: diseases & disorders > cancer
diseases & disorders
diseases & disorders > cancer > cancer types > breast cancer
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Dos Santos lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 26 March 2026
Date Deposited: 22 May 2026 12:09
Last Modified: 22 May 2026 12:09
PMCID: PMC13183921
Related URLs:
URI: https://repository.cshl.edu/id/eprint/42205

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