Khellin Modulates DDIT4 to Regulate Autophagy in Triple-Negative Breast Cancer

DDIT4 was considerably elevated after Khellin treatment, and higher expression was associated with a better prognosis in TNBC patients. Immune infiltration and single-cell transcriptome analysis demonstrated that elevated DDIT4 expression improves anti-tumor immune activity in the tumor microenvironment. Khellin administration increased the LC3B-II/I ratio and decreased P62 protein production, which could be reversed by autophagy inhibitors.

Conclusion: Khellin upregulates DDIT4 to activate autophagy in TNBC cells and remodel the tumor immune microenvironment. This study elucidates the critical function of DDIT4 in mediating Khellin-induced autophagy and immune modulation, laying the groundwork for a better understanding of its antitumor effects.