The Role of the mTOR Pathway in Cancer Stem Cells in Esophageal Cancer

Despite recent advances in the treatment of esophageal cancer (EC) using neoadjuvant chemoradiotherapy (CRT) and esophagectomy, most patients achieve poor outcomes, and growing evidence suggests that cancer stem cells (CSCs) might contribute to the poor prognosis. CSCs are usually resistant to CRT and ultimately can contribute to the formation of a new tumor. The mammalian target of rapamycin (mTOR) pathway is associated with cancer stemness. However, its role in EC CSC-like populations needs to be elucidated. In their presentation, Wang and colleagues investigated the role of mTOR pathway on the stemness of a putative CSC-like population.1

 

The authors had previously identified a putative CSC-like population (CD44+/CD24-) in EC cell lines and in tumor biopsy from EC patients. Quantitative polymerase chain reaction (qPCR) was used to measure the expression of mTOR in the CD44+/CD24- CSC-like population of OE21 esophageal squamous cell carcinoma and OE33 esophageal adenocarcinoma cell lines compared to controls.. In this presentation, the mTOR inhibitors rapamycin and Torin-1 were used to evaluate their effect on CD44+/CD24- expression and sphere formation. 

 

mTOR expression was 2-fold up-regulated in the OE33 CD44+/CD24- CSC-like population and 1.9-fold upregulated in OE21 squamous cell carcinoma cells compared to control cells. Surprisingly, inhibiting the mTOR pathway with 10 nM rapamycin enhanced OE33 CD44+/CD24- expression compared to its control (P = 0.01). Rapamycin did not alter the expression of CD44+/CD24- in OE21. Inhibiting the mTOR pathway with Torin-1 enhanced OE21 CD44+/CD24- expression by 1.2-fold compared to controls. Torin-1 did not have an effect on the expression of CD44+/CD24- in OE33. The authors concluded that inhibiting the mTOR pathway may enhance CSC-like populations in OE33 and OE21 cell lines.. Additional research is needed to support this hypothesis and elucidate and reverse this mechanism.. Furthermore, the effect of mTOR pathway inducers in EC needs to be further explored.

 

  1. Wang D, et al. ASCO 2016 Gastrointestinal Cancers Symposium. Abstract 43.