xCT/SLC7A11 Cancer Research Results

xCT/SLC7A11, Solute Carrier Family 7 Member 11: Click to Expand ⟱
Source:
Type: protein
SLC7A11 (also known as xCT) xenobiotic transporter.
XCT (xenobiotic transporter) is a protein that plays a crucial role in the transport of xenobiotics, including chemotherapeutic agents, across cell membranes.
xCT overexpressed in: breast, lung, colon, prostate, GBM, Pancreatic (with poor prognosis) Cancer cells often experience high levels of oxidative stress; upregulation of SLC7A11 helps to counteract this stress and supports cell survival.

Targeting SLC7A11 can sensitize tumor cells to oxidative damage and ferroptosis, offering a potential therapeutic avenue.

SLC7A11 encodes the light chain subunit of the cystine/glutamate antiporter system X_c⁻. This transporter imports cystine into the cell and exports glutamate out. The imported cystine is then used to synthesize glutathione (GSH), a major antioxidant that helps control intracellular ROS levels.

Many cancer cells experience elevated oxidative stress due to increased metabolic activity and stress conditions within the tumor microenvironment. Upregulation of SLC7A11 can provide a survival advantage by boosting GSH synthesis, thereby neutralizing ROS and preventing oxidative damage.

High SLC7A11 activity helps prevent ferroptosis by ensuring continuous glutathione production. Glutathione is a cofactor for glutathione peroxidase 4 (GPX4), a key enzyme that detoxifies lipid peroxides.
Mechanism: When SLC7A11 is inhibited, cystine uptake is reduced. This leads to glutathione depletion, compromised GPX4 activity, and eventually the accumulation of lipid peroxides that trigger ferroptosis.
Inducing ferroptosis has become a promising anticancer strategy. Inhibitors targeting SLC7A11 (or related pathways) can lower glutathione levels, increasing susceptibility to ferroptotic cell death. This is especially attractive in cancers with high SLC7A11 expression, where blocking its function may selectively induce ferroptosis and overcome drug resistance.
Scientific Papers found: Click to Expand⟱
5263- 3BP,  CET,    3-Bromopyruvate overcomes cetuximab resistance in human colorectal cancer cells by inducing autophagy-dependent ferroptosis
- in-vitro, CRC, DLD1 - NA, NA, HCT116
eff↑, Our results demonstrated that the co-treatment of 3-BP and cetuximab synergistically induced an antiproliferative effect in both CRC cell lines
Ferroptosis↓, co-treatment induced ferroptosis, autophagy, and apoptosis.
TumAuto↑,
Apoptosis↑,
FOXO3↑, co-treatment inhibited FOXO3a phosphorylation and degradation and activated the FOXO3a/AMPKα/pBeclin1 and FOXO3a/PUMA pathways, leading to the promotion of ferroptosis, autophagy, and apoptosis in DLD-1
AMPKα↑,
p‑Beclin-1↑,
HK2↓, 3-Bromopyruvate (3-BP), also known as hexokinase II inhibitor II, has shown promise as an anticancer agent against various types of cancer
ATP↓, 3-BP exerts its anticancer effects by manipulating cell energy metabolism and regulating oxidative stress, as evidenced by the accumulation of reactive oxygen species (ROS) [13,14,15,16].
ROS↑,
Dose↝, Eight days postinoculation, xenografted mice were randomly divided into four groups and intraperitoneally injected with PBS, 3-BP, cetuximab, or a combination of 3-BP and cetuximab every four days for five injections.
TumVol↓, 3-BP alone or co-treatment with 3-BP and cetuximab significantly reduced the tumor volume and tumor weight on Day 28, but co-treatment showed a greater reduction than 3-BP alone
TumW↓,
xCT/SLC7A11↑, The protein level of SLC7A11 was significantly upregulated in all three cell lines following co-treatment (Fig. 2B).
GSH↓, co-treatment with 3-BP and cetuximab led to glutathione (GSH) depletion (Fig. 2D), reactive oxygen species (ROS) production
eff↓, Knockdown of either ATG5 or Beclin1 attenuated the cell death and MDA production induced by co-treatment
MDA↑,

6983- Form,    Formononetin enhances angiogenesis in diabetic wounds by inhibiting ferroptosis through suppression of mtROS-mediated xCT/GPX4 upregulation
- vitro+vivo, Nor, HUVECs - vitro+vivo, Diabetic, NA
*BloodF↑, Formononetin (FMN), a phytoestrogen from Astragalus roots, is traditionally used to enhance blood function and microcirculation; however, its mechanism remains unclear.
*Ferroptosis↓, FMN effectively reduced ferroptosis markers in HG-treated HUVECs,
*eff↓, and Erastin treatment abolished this protective effect.
*mtDam↓, block ferroptosis through two mechanisms: restoration of mitochondrial integrity and reactivation of the xCT/GPX4 antioxidant system
*xCT/SLC7A11↑,
*GPx4↑,
*Wound Healing↑, When we tested FMN in diabetic mice, wound closure rates improved substantially, the expression of xCT and GPX4 was increased, and CD31 expression in wound vessels increased, which matched what we observed in vitro.
*CD31/PECAM-1↑,
*mt-ROS↓, mitigation of mitochondrial reactive oxygen species (mtROS) accumulation through xCT/GPX4 activation.

7766- ISL,    Isoliquiritigenin alleviates myocardial ischemia-reperfusion injury by regulating the Nrf2/HO-1/SLC7a11/GPX4 axis in mice
- in-vivo, Stroke, NA
*ROS↓, ISL significantly attenuated H/R-triggered production of reactive oxygen species in NMCM, reduced the expression of malondialdehyde and the activity of lactate dehydrogenase, enhanced superoxide dismutase and catalase activity,
*MDA↓,
*LDH↑,
*SOD↑,
*Catalase↑,
*NRF2↑, and increased the expression of nuclear factor E2-related factor 2 (Nrf2) and its downstream heme oxygenase 1 (HO-1), thereby mitigating oxidative stress damage.
*i-Iron↓, ISL reduced intracellular free iron accumulation, up-regulated glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression, and inhibited lipid peroxidation accumulation, thereby alleviating ferroptosis.
*GPx4↑,
*xCT/SLC7A11↑,
*lipid-P↓,
*Ferroptosis↓,
*HO-1↑, ISL treatment increased the levels of HO-1, GPX4, and SLC7A11, inhibited the expression of ACSL4
*ACSL4↓,
*mtDam↓, alleviated mitochondrial damage, and ferroptosis, ultimately reducing myocardial infarction area and injury induced by I/R.
*Stroke↓,

5096- SSE,    Selenium Toxicity Accelerated by Out-of-Control Response of Nrf2-xCT Pathway
- in-vitro, BC, MCF7
xCT/SLC7A11↑, Expression of xCT mRNA was remarkably increased in MCF-7 cells after Se treatment, which may further increase Se uptake and oxidative stress.
ROS↑,
NRF2↑, Oxidative stress activates Nrf2 regulon containing GSH biosynthesis enzymes and xCT. Therefore, further Se is taken into the cell, more ROS is generated, and xCT is induced again.

5094- SSE,    Sodium Selenite Prevents Matrine-Induced Nephrotoxicity by Suppressing Ferroptosis via the GSH-GPX4 Antioxidant System
- vitro+vivo, Nor, NRK52E
*GPx4↑, SS also reversed the MT-induced reduction in GPX4, CTH and xCT protein levels.
*xCT/SLC7A11↑,
*GSH↑, SS is a promising therapeutic drug for alleviating MT-induced renal injury by activating the GSH-GPX4 axis.
*RenoP↑,


Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress(tgid=1) ⓘ

Ferroptosis↓, 1,   GSH↓, 1,   MDA↑, 1,   NRF2↑, 1,   ROS↑, 2,   xCT/SLC7A11↑, 2,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

HK2↓, 1,  

Cell Death(tgid=5) ⓘ

Apoptosis↑, 1,   Ferroptosis↓, 1,  

Kinase & Signal Transduction(tgid=6) ⓘ

AMPKα↑, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

p‑Beclin-1↑, 1,   TumAuto↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

FOXO3↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 1,   eff↓, 1,   eff↑, 1,  

Functional Outcomes(tgid=23) ⓘ

TumVol↓, 1,   TumW↓, 1,  
Total Targets: 19

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

Stroke↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

Catalase↑, 1,   Ferroptosis↓, 2,   GPx4↑, 3,   GSH↑, 1,   HO-1↑, 1,   i-Iron↓, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 1,   mt-ROS↓, 1,   SOD↑, 1,   xCT/SLC7A11↑, 3,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

mtDam↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ACSL4↓, 1,   LDH↑, 1,  

Cell Death(tgid=5) ⓘ

Ferroptosis↓, 2,  

Migration(tgid=13) ⓘ

CD31/PECAM-1↑, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

eff↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

BloodF↑, 1,   LDH↑, 1,  

Functional Outcomes(tgid=23) ⓘ

RenoP↑, 1,   Wound Healing↑, 1,  
Total Targets: 24

Scientific Paper Hit Count for: xCT/SLC7A11, Solute Carrier Family 7 Member 11
2 Selenite (Sodium)
1 3-bromopyruvate
1 cetuximab
1 Formononetin
1 Isoliquiritigenin
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:801  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

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