Data from Nicotine-Induced ILF2 Facilitates Nuclear mRNA Export of Pluripotency Factors to Promote Stemness and Chemoresistance in Human Esophageal Cancer

• DOI: 10.1158/0008-5472.c.6512935.v1
• Publication Date: 2023-03-31T21:28:23Z
• Authors: Yue Li; Meng Wang; Muwen Yang; Yunyun Xiao; Yunting Jian; Dongni Shi; Xiangfu Chen; Ying Ouyang; Lingzhi Kong; Xinjian Huang; Jiewen Bai; Yameng Hu; Chuyong Lin; Libing Song
• Keywords: Homeobox protein NANOG; Nuclear export signal

<div>Abstract<p>Balancing mRNA nuclear export kinetics with its decay is critical for homeostasis control. How this equilibrium aberrantly disrupted in esophageal cancer to acquire stem cell properties remains unclear. Here we find that the RNA-binding protein interleukin enhancer binding factor 2 (ILF2) robustly upregulated by nicotine, a major chemical component of tobacco smoke, via activation JAK2/STAT3 signaling and significantly correlates poor prognosis heavy-smoking patients cancer. ILF2 bound THO complex THOC4 as regulatory cofactor induce selective interactions pluripotency transcription mRNAs promote their assembly into export-competent messenger ribonucleoprotein complexes. facilitated inhibited hMTR4-mediated exosomal degradation stabilization expression SOX2, NANOG, SALL4, resulting enhanced stemness tumor-initiating capacity cells. Importantly, inducible depletion increased therapeutic efficiency cisplatin abrogated nicotine-induced chemoresistance <i>in vitro</i> vivo</i>. These findings reveal novel role maintenance cells open new avenues overcome smoking-mediated cancer.</p>Significance:<p>This study defines previously uncharacterized nicotine-regulated facilitating stemness, suggesting potential strategy against cancer.</p></div>