Ectopic Expression of a Truncated Isoform of Hair Keratin 81 in Breast Cancer Alters Biophysical Characteristics to Promote Metastatic Propensity

The study investigated the role of a truncated isoform of Hair Keratin 81 (tKRT81) in breast cancer metastasis. Researchers found that tKRT81 is upregulated in metastatic derivatives of circulating tumor cells (CTCs) and its high expression is linked to shorter lung and brain metastasis-free survival in breast cancer patients. High tKRT81 expression was also associated with decreased survival probability and was over-represented in the basal subtype of breast cancer. The study found that tKRT81 interacts with keratin 18 (KRT18), disrupting intermediate filament organization in breast cancer cells, altering desmosome structure, increasing cluster formation, and enhancing cell adhesion to collagen and transendothelial migration. Knockdown of tKRT81 led to an increase in cell stiffness and a decrease in cell and nuclear size. In immune-deficient mouse models, tKRT81 was upregulated in lung metastases generated from patient-derived CTC lines. High tKRT81 expression was associated with poor survival in breast cancer patients. The study suggests that tKRT81 plays a significant role in cancer metastasis and could be a potential target for cancer treatment.