Abstract 1227: Esophageal cancer shows spontaneous plasticity between epithelial and mesenchymal status

Abstract Epithelial-mesenchymal transition (EMT) is one of essential processes in cancer progression. Plasticity between epithelial and mesenchymal status is referred as epithelial-mesenchymal plasticity (EMP). The significance of spontaneous change of EMP is under investigation in the field of EMT. To date, spontaneous EMP is reported in breast and prostate cancer, which leads to the acquisition of stem-cell properties and chemoresistance. On the other hand, the presence of spontaneous EMP is still not examined in other cancer including esophageal cancer. In the present study, we tackled the question of whether esophageal cancer have the potency of spontaneous EMP. We screened eleven esophageal squamous cancer cell (ESCC) cell lines with CD44 isoform expression, which is known to reflect epithelial and mesenchymal status. Interestingly, KYSE520 was found to comprise heterogenous populations consisting of CD44v+ and CD44v- subpopulations. CD44v+ and CD44v- cells showed the expression of epithelial and mesenchymal markers, respectively. Single-cell sorting of CD44v+ and CD44v- cells revealed both cells gave rise to cell populations consisting of CD44v+ and CD44v- cells, indicating CD44v+ epithelial-like and CD44v- mesenchymal-like cells can generate counterparts, respectively. This EMP was maintained in next generation. Further, we found the generation of counterparts between CD44v+ and CD44v- cells in vivo. Epithelial splicing regulatory protein 1 (ESRP1) is reported as the regulator of CD44 mRNA splicing. The role of ESRP1 in EMP is not well understood in esophageal cancer. The inhibition of ESRP1 shifted CD44v+ to CD44v- cells in KYSE520. However, the expression of epithelial-mesenchymal transition (EMT)-related markers or transcriptional factors were almost not affected, suggesting ESRP1 functions downstream of EMP. Our results firstly revealed the presence of spontaneous EMP in esophageal cancer and give a new insight in the field of EMT. Citation Format: Kenji Tsuchihashi, Yuki Hirata, Juntaro Yamasaki, Kentaro Suina, Kenro Tanoue, Toshifumi Yae, Kenta Masuda, Eishi Baba, Koichi Akashi, Yuko Kitagawa, Hideyuki Saya, Osamu Nagano. Esophageal cancer shows spontaneous plasticity between epithelial and mesenchymal status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1227.