Ferroptosis Target Information

General Information of the Ferroptosis Target (ID: TAR10045)
Target Name Monocarboxylate transporter 1 (SLC16A1)
Synonyms
Solute carrier family 16 member 1
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Gene Name SLC16A1
Sequence
MPPAVGGPVGYTPPDGGWGWAVVIGAFISIGFSYAFPKSITVFFKEIEGIFHATTSEVSW
ISSIMLAVMYGGGPISSILVNKYGSRIVMIVGGCLSGCGLIAASFCNTVQQLYVCIGVIG
GLGLAFNLNPALTMIGKYFYKRRPLANGLAMAGSPVFLCTLAPLNQVFFGIFGWRGSFLI
LGGLLLNCCVAGALMRPIGPKPTKAGKDKSKASLEKAGKSGVKKDLHDANTDLIGRHPKQ
EKRSVFQTINQFLDLTLFTHRGFLLYLSGNVIMFFGLFAPLVFLSSYGKSQHYSSEKSAF
LLSILAFVDMVARPSMGLVANTKPIRPRIQYFFAASVVANGVCHMLAPLSTTYVGFCVYA
GFFGFAFGWLSSVLFETLMDLVGPQRFSSAVGLVTIVECCPVLLGPPLLGRLNDMYGDYK
YTYWACGVVLIISGIYLFIGMGINYRLLAKEQKANEQKKESKEEETSIDVAGKPNEVTKA
AESPDQKDTDGGPKEEESPV

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Family Major facilitator superfamily
Function
Bidirectional proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, acetate and the ketone bodies acetoacetate and beta-hydroxybutyrate, and thus contributes to the maintenance of intracellular pH . The transport direction is determined by the proton motive force and the concentration gradient of the substrate monocarboxylate. MCT1 is a major lactate exporter. Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis. Facilitates the protonated monocarboxylate form of succinate export, that its transient protonation upon muscle cell acidification in exercising muscle and ischemic heart. Functions via alternate outward- and inward-open conformation states. Protonation and deprotonation of 309-Asp is essential for the conformational transition.

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Gene ID 6566
Uniprot ID
P53985
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Tissue Relative Abundances of This Target
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
SLC16A1 can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
Browse Regulator related Drug
Unspecific Regulator
Hepatocellular carcinoma [ICD-11: 2C12]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Responsed Drug Lactate Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 CAF cells Normal Carassius auratus CVCL_R883
HEK-293T cells Normal Homo sapiens CVCL_0063
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable.

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Response Description Lactate regulates the ferroptosis of hepatocellular carcinoma cells. And blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 (SLC16A1) inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility.
Ovarian cancer [ICD-11: 2C73]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [2]
Responsed Drug NL01 Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Anglne cells Ovarian carcinoma Homo sapiens CVCL_U287
HO8910PM cells Endocervical adenocarcinoma Homo sapiens CVCL_0310
In Vivo Model
BALB/c Nude female mice were adjusted for 7 days in a SPF room and divided into 2 groups (6 mice per group): DMSO and NL01 (5 mg/kg). NL01 was dissolved in 1% carboxymethylcellulose (Millipore, USA). DMSO (control) used the same volume of vehicle (1% carboxymethylcellulose). HO8910PM cells were grown in tissue culture, and counted. 1 x 106 cells were inoculated to subcutaneously. Ten days after inoculation, the drugs were administered every five days subcutaneously to the mice for 15 days.

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Response Description NL01 induced iron death and inhibited ovarian cancer proliferation. NL01 was able to reduce the expression of HCAR1/MCT1 (SLC16A1) and activate the AMPK signaling pathway in ovarian cancer cells, which in turn induced cellular ferroptosis via SREBP1 (SREBF1) pathway. SCD1 (Stearoyl-CoA desaturase-1) is the downstream target of SREBP1. Further study showed that NL01 promoted the downregulation of GPX4 expression.
Unspecific Regulator
Lactate [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [1]
Responsed Disease Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CAF cells Normal Carassius auratus CVCL_R883
HEK-293T cells Normal Homo sapiens CVCL_0063
L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
In Vivo Model
Female mice aged around 6-7 weeks were used for this study, which were purchased through Laboratory Animal Center of Chongqing Medical University from Vital River Co. Ltd (Beijing, China).After one week, each mouse was injected subcutaneously with 100 uL of Huh-7 cell suspension (5 x 106 units) to establish the tumor model. The mice were grouped randomly, and then subjected to different treatments after subcutaneous tumors became visually detectable.

    Click to Show/Hide
Response Description Lactate regulates the ferroptosis of hepatocellular carcinoma cells. And blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 (SLC16A1) inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility.
NL01 [Investigative]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the Ferroptosis-centered Drug Response of This Regulator [2]
Responsed Disease Ovarian cancer [ICD-11: 2C73]
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
AMPK signaling pathway hsa04152
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Anglne cells Ovarian carcinoma Homo sapiens CVCL_U287
HO8910PM cells Endocervical adenocarcinoma Homo sapiens CVCL_0310
In Vivo Model
BALB/c Nude female mice were adjusted for 7 days in a SPF room and divided into 2 groups (6 mice per group): DMSO and NL01 (5 mg/kg). NL01 was dissolved in 1% carboxymethylcellulose (Millipore, USA). DMSO (control) used the same volume of vehicle (1% carboxymethylcellulose). HO8910PM cells were grown in tissue culture, and counted. 1 x 106 cells were inoculated to subcutaneously. Ten days after inoculation, the drugs were administered every five days subcutaneously to the mice for 15 days.

    Click to Show/Hide
Response Description NL01 induced iron death and inhibited ovarian cancer proliferation. NL01 was able to reduce the expression of HCAR1/MCT1 (SLC16A1) and activate the AMPK signaling pathway in ovarian cancer cells, which in turn induced cellular ferroptosis via SREBP1 (SREBF1) pathway. SCD1 (Stearoyl-CoA desaturase-1) is the downstream target of SREBP1. Further study showed that NL01 promoted the downregulation of GPX4 expression.
References
Ref 1 HCAR1/MCT1 Regulates Tumor Ferroptosis through the Lactate-Mediated AMPK-SCD1 Activity and Its Therapeutic Implications. Cell Rep. 2020 Dec 8;33(10):108487. doi: 10.1016/j.celrep.2020.108487.
Ref 2 Curcumin derivative NL01 induces ferroptosis in ovarian cancer cells via HCAR1/MCT1 signaling. Cell Signal. 2023 Sep;109:110791. doi: 10.1016/j.cellsig.2023.110791. Epub 2023 Jul 3.