TRIM9 Interacts with ZEB1 to Suppress Esophageal Cancer by Promoting ZEB1 Protein Degradation via the UPP Pathway

Abstract

Background. Esophageal cancer remains one of the most lethal malignant diseases globally. Previous studies indicated that TRIM9 (Tripartite Motif Containing 9) is a potential marker in breast cancer patients. Therefore, in the current research, we intended to clarify the regulatory network of TRIM9 and its relative role in esophageal cancer patients. We aimed to elucidate the regulatory role of TRIM9 in esophageal cancer. Methods. Clinical tumor tissue samples combined with cancer cell line models were utilized to explore the TRIM9 expression pattern. Functional experiments including transwell assay, cell viability assay, and ubiquitination blocking experiments were performed to evaluate the role of the TRIM9/ZEB1 (zinc finger E-box binding homeobox 1) axis and UPP pathway in esophageal cancer progression and exacerbation. Results. Both esophageal cancer samples and cell line models showed significantly suppressed levels of TRIM9. Functional experiments confirmed that TRIM9 overexpression inhibited the cell viability, invasiveness, and stem-like phenotype of cancer cells. Subsequent investigations suggested that TRIM9-ZEB1 interaction accelerated ZEB1 protein degradation through the modulation of the UPP pathway, which confirmed the protective role of TRIM9 in esophageal cancer progression and metastasis. Conclusion. This study concluded that TRIM9 was a tumor suppressor that interacted with ZEB1 and accelerated ZEB1 protein degradation via the ubiquitin-proteasome pathway (UPP). Our research emphasized TRIM9-ZEB1 interaction as a valuable target for esophageal cancer treatment in future development. More detailed studies are needed to further consolidate our findings.

Multi-monoubiquitylation controls VASP-mediated actin dynamics

“…TRIM9 has been studied primarily in the context of neuronal development and neurodegeneration ( Menon et al, 2015 ; Boyer et al, 2020 ; Plooster et al, 2017 ; Tanji et al, 2010 ; Winkle et al, 2016 ; Zeng et al, 2019 ; Do et al, 2018 ). However, TRIM9 is also expressed in macrophages ( Tokarz et al, 2017 ; Carthagena et al, 2009 ) and various forms of cancers ( Yang et al, 2020 ; Lin et al, 2023 ; Zhang et al, 2023 ; Mishima et al, 2015 ). Although the alteration of TRIM9 protein levels has been shown to affect cell proliferation, motility and inflammation in cell lines, substrates of TRIM9 have not been identified in these studies.…”

Multi-monoubiquitination controls VASP-mediated actin dynamics

“…TRIM9 has been studied primarily in the context of neuronal development and neurodegeneration (Menon et al, 2015;Boyer et al, 2020;Plooster et al, 2017;Tanji et al, 2010;Winkle et al, 2016;Zeng et al, 2019;Winkle et al, 2016;Do et al, 2018). However, TRIM9 is also expressed in macrophages (Tokarz et al, 2017;Carthagena et al, 2009) and various forms of cancer (Yang et al, 2020a;Lin et al, 2023;Zhang et al, 2023;Mishima et al, 2015). Although the alteration of TRIM9 protein levels has been shown to affect cell proliferation, motility, and inflammation in cell lines, substrates of TRIM9 have not been identified in these studies.…”