Cell Death Database

RNA Name: PIK3C3

Mechanism of Action: Class III PI3K (VPS34) generates PI3P to initiate autophagosome formation; pharmacologic inhibition blocks autophagy.

Effect on Cancer: In TNBC cell lines, VPS34 inhibition with SAR405 altered immunogenic signaling and activated NF-?B/CXCL10; highlights autophagy�s role in TNBC response.

PMID: 40691137

RNA Name: ATP7A

Mechanism of Action: Copper-exporting ATPase ATP7A reduces intracellular copper and can blunt cuproptosis by exporting toxic copper.

Effect on Cancer: ATP7A supports copper-dependent enzymes (e.g., LOX) that promote invasion/metastasis in breast cancer; modulating ATP7A or copper levels affects metastasis and cuproptosis sensitivity.

PMID: 30890638

RNA Name: CDKN2A

Mechanism of Action: CDKN2A (p16INK4a/p14ARF locus) was associated with modifiers of cuproptosis in genomic screens and may affect cell-state dependent sensitivity.

Effect on Cancer: CDKN2A status may modulate cuproptosis susceptibility and therapy response in breast cancer.

PMID: 39976173

RNA Name: FDX1

Mechanism of Action: FDX1 (ferredoxin 1) is a core cuproptosis regulator that promotes protein lipoylation and sensitizes cells to copper-induced DLAT oligomerization and proteotoxic stress.

Effect on Cancer: In TNBC models, FDX1 activity/state is linked to cuproptosis sensitivity and tumor growth: AKT1 phosphorylation of FDX1 was reported to mediate cuproptosis resistance in TNBC, and FDX1 knockdown reduced tumor growth and affected CD8?? T-cell responses.

PMID: 40911146

RNA Name: DLAT

Mechanism of Action: lipoylated and, upon copper binding/oligomerization, undergoes toxic aggregation that is central to cuproptosis execution.

Effect on Cancer: targeting DLAT-dependent processes sensitizes TNBC cells to copper ionophores.

PMID: 39460738

RNA Name: LIPT1

Mechanism of Action: Required for protein lipoylation and the DLAT-dependent proteotoxic aggregation that defines cuproptosis.

Effect on Cancer: Multiple bioinformatic and review papers report differential expression or prognostic associations of these genes in breast cancer / TNBC and propose that their expression/state determines cuproptosis susceptibility; experimental TNBC validation is emerging.

PMID: 37853210

RNA Name: DLD

Mechanism of Action: Required for protein lipoylation and the DLAT-dependent proteotoxic aggregation that defines cuproptosis.

Effect on Cancer: Multiple bioinformatic and review papers report differential expression or prognostic associations of these genes in breast cancer / TNBC and propose that their expression/state determines cuproptosis susceptibility; experimental TNBC validation is emerging.

PMID: 37853210

RNA Name: PDHA1

Mechanism of Action: Required for protein lipoylation and the DLAT-dependent proteotoxic aggregation that defines cuproptosis.

Effect on Cancer: Multiple bioinformatic and review papers report differential expression or prognostic associations of these genes in breast cancer / TNBC and propose that their expression/state determines cuproptosis susceptibility; experimental TNBC validation is emerging.

PMID: 37853210

RNA Name: ATP7B

Mechanism of Action: Copper efflux pump ATP7B modulates cellular copper homeostasis and can decrease cuproptosis susceptibility.

Effect on Cancer: Reported in pan-cancer/cuproptosis signatures and may contribute to therapy resistance via copper handling in breast tumors.

PMID: 37853210

RNA Name: SLC31A1

Mechanism of Action: Copper importer (CTR1) increases cellular copper uptake, promoting susceptibility to cuproptosis when mitochondrial lipoylated proteins are overloaded.

Effect on Cancer: Upregulated in breast cancer and associated with worse prognosis; part of proposed LINC01640/miR-204-5p?SLC31A1 cuproptosis axis.

PMID: 37884650