scholarly journals SLC6A14 (ATB0,+) Protein, a Highly Concentrative and Broad Specific Amino Acid Transporter, Is a Novel and Effective Drug Target for Treatment of Estrogen Receptor-positive Breast Cancer

2011 ◽  
Vol 286 (36) ◽  
pp. 31830-31838 ◽  
Author(s):  
Senthil Karunakaran ◽  
Sabarish Ramachandran ◽  
Veena Coothankandaswamy ◽  
Selvakumar Elangovan ◽  
Ellappan Babu ◽  
...  
2018 ◽  
Author(s):  
Raksha Bhat ◽  
Suhas Vasaikar ◽  
Leon Bae ◽  
De Angelis Carmine ◽  
Maria Letizia Cataldo ◽  
...  

2021 ◽  
Vol 22 (13) ◽  
pp. 6706
Author(s):  
Chelsea Thompson ◽  
M Motiur Rahman ◽  
Soudamani Singh ◽  
Subha Arthur ◽  
Cecilia Sierra-Bakhshi ◽  
...  

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 3H-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.


2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Ryan J O Dowling ◽  
Kevin Kalinsky ◽  
Daniel F Hayes ◽  
Francois-Clement Bidard ◽  
David W Cescon ◽  
...  

Abstract Disease recurrence (locoregional, distant) exerts a significant clinical impact on the survival of estrogen receptor–positive breast cancer patients. Many of these recurrences occur late, more than 5 years after original diagnosis, and represent a major obstacle to the effective treatment of this disease. Indeed, methods to identify patients at risk of late recurrence and therapeutic strategies designed to avert or treat these recurrences are lacking. Therefore, an international workshop was convened in Toronto, Canada, in February 2018 to review the current understanding of late recurrence and to identify critical issues that require future study. In this article, the major issues surrounding late recurrence are defined and current approaches that may be applicable to this challenge are discussed. Specifically, diagnostic tests with potential utility in late-recurrence prediction are described as well as a variety of patient-related factors that may influence recurrence risk. Clinical and therapeutic approaches are also reviewed, with a focus on patient surveillance and the implementation of extended endocrine therapy in the context of late-recurrence prevention. Understanding and treating late recurrence in estrogen receptor–positive breast cancer is a major unmet clinical need. A concerted effort of basic and clinical research is required to confront late recurrence and improve disease management and patient survival.


JAMA Oncology ◽  
2020 ◽  
Vol 6 (2) ◽  
pp. 301
Author(s):  
Steven A. Narod ◽  
Vasily Giannakeas ◽  
Victoria Sopik

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