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ATP-binding cassette transporter sub-family C member 11 (ABCC11)

Target: ABCC11
Molecular classification: Transporter, ATP-binding cassette (ABC) transporter, Multidrug resistance-associated protein (MRP) family member

Overview

ATP-binding cassette transporter sub-family C member 11 (ABCC11/MRP8) is a membrane protein belonging to the MRP family of ABC transporters. It functions as an ATP-dependent exporter of a variety of endogenous and xenobiotic organic anions, including conjugated steroids, bile acids, folates, cyclic nucleotides, and chemotherapeutic drug metabolites. ABCC11 is distinct for its role in determining human cerumen phenotype and body odor, and is highly expressed in certain hormone-regulated tissues and cancers. Its substrates and expression patterns implicate it in drug resistance, steroid hormone response, and physiological secretions. Increased expression is associated with poor survival in specific cancers, highlighting significance as both a therapeutic target and a biomarker.

Other names: Multidrug Resistance-Related Protein 8 (MRP8)ABCC11ATP-binding cassette transporter sub-family C member 11

Mechanism of action

Drugs targeting this transporter typically act by inhibiting or modulating the protein’s ATP-dependent transport activity, thereby altering efflux of drugs/metabolites from cells and reversing drug resistance. Efflux of conjugated drugs or metabolites reduces intracellular concentration, causing resistance to chemotherapy.

Biological functions

Cellular export of organic anions and conjugated metabolitesDrug resistance via efflux of chemotherapeutic agentsRegulation of bile acid and steroid hormone conjugate transportDetermination of physiological traits (e.g., human earwax type, axillary odor)Maintenance of cyclic nucleotide homeostasis (export of cAMP, cGMP)

Disease associations

Cancer (especially breast cancer and acute myelogenous leukemia)Drug resistance in cancer therapyAssociated with variation in ear wax and axillary body odor (not a disease in classical sense)Potential biomarker for cancer prognosis (AML, breast cancer)Other: possible implications in colostrum secretion

Safety considerations

Inhibition of ABCC11/MRP8 may increase sensitivity to chemotherapeutics, but could also disrupt physiological transport of bile acids, steroid conjugates, and cyclic nucleotides, potentially affecting hormone regulation, hepatic function, and homeostasisGenetic variation may have unintended phenotypic consequences (e.g., ear wax, body odor)Overexpression may contribute to multidrug resistance in cancer, reducing chemotherapy efficacy

Interacting drugs

Methotrexate (MTX)

8 more in the full profile.

Biomarkers

Overexpression in tumors, especially breast cancer and AML, is a potential biomarker of poor prognosis or multidrug resistanceSNPs determining cerumen type and body odor

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