The Adipose Tissue-Derived Secretome (ADS) in Obesity Uniquely Induces L-Type Amino Acid Transporter 1 (LAT1) and mTOR Signaling in Estrogen-Receptor-Positive Breast Cancer Cells
Thompson C., Rahman MM., Singh S., Arthur S., Sierra-Bakhshi C., Russell R.
Prospective Study, published in Int J Mol Sci (2021) — summary generated from the PubMed abstract.
Early human evidence such as case series or small samples is exploring possible benefits.
- Level A · Stronger Clinical Evidence
- Level B · Emerging clinical evidence with positive signals
- Level C · Early human research exploring benefits
- Level D · Scientific groundwork from lab and animal studies
- Emerging · Emerging topic under active research
This page is generated from the PubMed record. The Thai description is an automated summary of bibliographic fields and the abstract, not a full translation, and is not medical advice.
- Study type
- Prospective Study
- Journal
- Int J Mol Sci (2021)
- Reported sample size
- —
- Source database
- Europe PMC
- PMID
- 34201429
- PMCID
- PMC8268498
- DOI
- 10.3390/ijms22136706
- Citations
- 11
Abstract (original English)
Obesity increases the risk of postmenopausal breast cancer (BC). This risk is mediated by obesity-induced changes in the adipose-derived secretome (ADS). The pathogenesis of BC in obesity is stimulated by mTOR hyperactivity. In obesity, leucine might support mTOR hyperactivity. Leucine uptake by BC cells is through L-Type Amino Acid Transporter 1 (LAT1). Our objective was to link obesity-ADS induction of LAT1 to the induction of mTOR signaling. Lean- and obese-ADS were obtained from lean and obese mice, respectively. Breast ADS was obtained from BC patients. Estrogen-receptor-positive BC cells were stimulated with ADS. LAT1 activity was determined by uptake of 3 H-leucine. The LAT1/CD98 complex, and mTOR signaling were assayed by Western blot. The LAT1 antagonists, BCH and JPH203, were used to inhibit LAT1. Cell migration and invasion were measured by Transwell assays. The results showed obese-ADS-induced LAT1 activity by increasing transporter affinity for leucine. Consistent with this mechanism, LAT1 and CD98 expression were unchanged. Induction of mTOR by obese-ADS was inhibited by LAT1 antagonists. Breast ADS from patients with BMIs > 30 stimulated BC cell migration and invasiveness. Collectively, our findings show that obese-ADS induction of LAT1 supports mTOR hyperactivity in luminal BC cells.
What this study does not prove
- • This study does not prove SVF is an approved treatment or a replacement for standard care.
Evidence level
Early human evidence such as case series or small samples is exploring possible benefits.
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