Abstract
The SLC7A5/SLC3A2 amino acid transporter moves essential amino acids, such as leucine, phenylalanine, and tryptophan, across the cellular plasma membrane. SLC7A5 overexpression was identified in diverse cancers, suggesting a role in tumorigenesis and cancer cell proliferation. However, the role of SLC7A5/SLC3A2 in other aggressive cellular phenotypes, including mesothelial mesenchymal transition (MesoMT), remains unexplored. RNA sequencing analyses identified SLC7A5 as one of three highly upregulated SLCs in mesothelial cell derived myofibroblasts. This sodium independent transporter exhibits a high affinity for branched chain amino acids such as leucine; however, what role, if any, this channel plays in MesoMT is unclear. SLC7A5 knockdown using targeting siRNA and siRNAs inhibited MesoMT induction as indicated by the reduced expression of aSMA and Col-1, markers of MesoMT. Similar results were found in SLC3A2 downregulated cells. Inhibition studies using specific SLC7A5 inhibitors, JPH203 and Compound #5, likewise significantly blunted induction of MesoMT. Paradoxically, the expression of SLC7A5 and its ancillary subunit SLC3A2 were increased when high concentrations of SLC7A5 inhibitor were used. These findings suggest a potential compensatory mechanism in response to reduced amino acid availability. Hence, we hypothesize that SLC7A5/SLC3A2 transporters are functionally active in HPMCs and may represent a therapeutic target for the treatment of pleural fibrosis.
Date of publication
2025
Document Type
Thesis
Language
english
Persistent identifier
http://hdl.handle.net/10950/4857
Committee members
Dr.Torry A Tucker, Dr. Amy R Tvinnereim, Dr. Vijay Rao, Dr. Hua Tang
Degree
Masters in Biotechnology
Recommended Citation
Francis, Ann, "CHARACTERIZATION OF THE SLC7A5/SLC3A2 AMINO ACID TRANSPORTER IN HUMAN PLEURAL MESOTHELIAL CELLS" (2025). Biotechnology Theses. Paper 28.
http://hdl.handle.net/10950/4857