Interaction mechanisms between autophagy and ferroptosis: Potential role in colorectal cancer

Table 1 The role of autophagy in colorectal cancer

Intervention	Target	Effects and mechanism	Ref.
Aspirin	mTOR↓, AMPK↑	Inhibits mTOR signal transduction and activates AMPK to induce autophagy of CRC	[33]
TBK1	mTORC1↓	TBK1 initiates mTORC1 inhibition and induces autophagy to promote CRC progression	[139]
ABHD5	BECN1↑	ABHD5 prevents CASP3 from cleaving BECN1 and enhances autophagy flux to inhibit CRC	[38]
SOX2	BECN1↑	SOX2-β-catenin/Beclin1/autophagy signaling axis promotes chemoresistance of CRC	[41]
FIRRE	Stabilize BECN1	Stabilizes BECN1 and promotes autophagy in a PTBP1 mediated manner to stimulate the development of CRC	[42]
IL-6	BECN1↑	IL-6/BECN1 pathway activates autophagy and promotes chemotherapy resistance of CRC	[39]
Pelareorep	BECN1↑	Upregulates BECN1 expression and induces autophagy to enhance CRC proliferation	[140]
Fusobacterium nucleatum	BECN1↑, CARD3↑	Upregulates CARD3 expression and activates autophagy signal to promote CRC metastasis	[141]
DCZ5248	p62↑	Induces lysosomal acidification and weakens lysosomal cathepsin activity to inhibit autophagy	[142]
Claudin 1	p62↓	Reduces the level of p62 and stimulates autophagy to promote CRC progression	[143]
DBTTS	p62↑	Induces accumulation of p62 protein and inhibits autophagy to induce CRC cell death	[47]

mTOR: The mammalian target of rapamycin; AMPK: Adenosine monophosphate-activated protein kinase; TBK1: TANK-binding kinase 1; mTORC1: mTOR complex 1; ABHD5: Abhydrolase domain containing 5; BECN1: Beclin1; CASP3: Caspase 3; SOX2: Sex-determining region Y-box2; FIRRE: Firre intergenic repeating RNA element; PTBP1: Polypyrimidine tract-binding protein; CARD3: Caspase activation and recruitment domain 3; DCZ5248: A heat shock protein 90 inhibitor; p62: Sequestosome 1; DBTTS: Diallyl tetrasulfide and its derivative, dibenzyl tetrasulfide; CRC: Colorectal cancer.

Table 2 The role of ferroptosis in colorectal cancer

Intervention	Target	Effects and mechanism	Ref.
SRSF9	GPX4↓	Inhibition of SRSF9 increases erastin-induced iron death by downregulation of GPX4 level	[74]
IMCA	SLC7A11↓	IMCA induces SLC7A11 mediated ferroptosis through AMPK/mTOR pathway	[77]
TalaA	ROS↑, SLC7A11↓	TalaA induces ferroptosis to kill CRC cells	[144]
Lipocalin 2	GPX4↑, system Xc−↑	Overexpression of Lipocalin 2 inhibits ferroptosis and promotes CRC progression	[75]
TIGAR	GSH↓, ROS↑	TIGAR induces ferroptosis resistance in CRC by ROS/AMPK/SCD1 signaling pathway	[145]
HIF-2α	Iron↑	HIF-2α activation potentiates oxidative cell death in CRCs by increasing cellular iron	[79]
TP53	Lipid peroxidation, ACSL4↑	Restricts ferroptosis by blocking DPP4 activity in a transcription independent manner TP53	[91]
Tagitinin C	NRF2/HO-1↑, lipid peroxidation	Tagitin C activates NRF2/HO-1 pathway to induce ferroptosis	[82]
Cetuximab	NRF2↓, ROS↑	Cetuximab inhibits Nrf2/HO-1 pathway to promote ferroptosis in CRC	[85]
Beta-elemene	GSH↓, GPX4↓	Combined treatment with beta-elemene and cetuximab induces ferroptosis in CRC	[96]
Vitamin C	Iron↑, ROS↑	Vitamin C limits CRC resistance to EGFR-targeted therapies	[97]
FeOOH NSs	H2S↓	FeOOH NSs eliminate endogenous H2S to induce ferroptosis	[99]

SRSF9: Serine and arginine rich splicing factor 9; GPX4: Glutathione peroxidase 4; IMCA: The benzopyran derivative 2-imino-6-methoxy-2H-chromene-3-carbothioamide; SLC7A11: Solute carrier family 7 member 11; TalaA: Talaroconvolutin A; ROS: Reactive oxygen species; TIGAR: TP53-induced glycolysis and apoptosis regulator; GSH: Glutathione; SCD1: Stearoyl-coenzyme A desaturase-1; HIF-2α: Hypoxia-inducible factor 2α; TP53: Tumor suppressor p53; ACSL4: Acyl-CoA synthetase long-chain family member 4; NRF2: Nuclear factor erythroid 2-related factor 2; HO-1: Haem oxygenase 1; DPP4: Dipeptidyl-peptidase-4; FeOOH NSs: Iron oxide-hydroxide nanospindles; CRC: Colorectal cancer.