Expression of CD44 is regulated by ELF3 in 5-FU treated colorectal cancer cells

The development of chemoresistance in colorectal cancer (CRC) cells was usually thought to be inevitable as a result of continuing exposure to chemotherapeutic drugs. The existence of cancer stem cells (CSCs) within CRC tissues was recently suggested to play importance roles for this process. In this study, in order to mimic a dose schedule used in clinic (continuous infusion), low dose of fluorouracil (IC₁₀ of 5-FU) was used to treat CRC cells. Our results showed that the expression of CD44, including some other CSCs markers were all increased after 5-FU treatment. The stemness properties of survived CRC cells were also observed to be enhanced. RNA-seq analysis revealed that ELF3, one of the members of ETS (E26 transformation-specific) transcription activator family, was increased along with CD44 after 5-FU treatment of CRC cells. Results from dual-luciferase reporter assay revealed that the transcription of CD44 could be activated by ELF3 in CRC cells. The induced CD44 expression in 5-FU treated CRC cells could also be decreased after the expression of ELF3 was inhibited. Moreover, it could be observed that the expression of ELF3 is significantly higher in CD44⁺ CRC cells. Taken together, our results suggested that CD44 expression might be regulated by ELF3 and could be induced after 5-FU treatment of CRC cells. Inhibition of ELF3 might be a promising treatment method when it was used in combination with chemotherapeutics to overcome chemoresistance formation during CRC treatment in clinic.