Abstract
Tripartite motif-containing protein 44 (TRIM44) was recently identified as a potential therapeutic target in several types of malignancy, but its effect on the clinical course of malignancy and its underlying regulatory mechanism remain largely unknown. The present study shows that upregulation of TRIM44 is associated with poor differentiation, advanced pTNM stage, adenocarcinoma subtype, lymph node metastasis and, most importantly, unfavorable survival in patients with non-small cell lung cancer (NSCLC). TRIM44 knockdown inhibited the invasion and migration of human NSCLC cells, which was concurrent with downregulation of mesenchymal markers and upregulation of epithelial markers. Overexpression of TRIM44 induced the epithelial-to-mesenchymal transition (EMT) and increased the metastatic potential of lung cancer cells. Additionally, TRIM44 induced cell proliferation in vitro and tumor growth in vivo by accelerating G1/S transition via upregulation of cyclins and CDKs. TRIM44-induced mTOR signaling, EMT, and cyclin/CDK upregulation were reversed by treatment with a mammalian target of rapamycin (mTOR) inhibitor. These results provide a model for the relationship between TRIM44 expression and lung cancer progression, and open up new avenues for the prognosis and therapy of lung cancer.
Highlights
Lung cancer is the leading cause of cancer‐related death worldwide, with nearly 1.4 million deaths recorded annually [1]
Consistent with this, the results revealed that the mean relative expression of Tripartite motif‐containing protein 44 (TRIM44) mRNA in tumor tissues from patients with lymph node metastasis was higher than that in tumor tissues from patients without lymph node metastasis (P = 0.034; Figure 1F)
We report that the expression of TRIM44 was significantly increased in tumor tissues from patients with Non‐small cell lung cancer (NSCLC)
Summary
Lung cancer is the leading cause of cancer‐related death worldwide, with nearly 1.4 million deaths recorded annually [1]. Non‐small cell lung cancer (NSCLC) accounts for 70–80% of all lung cancer cases, and nearly 50% of patients with stage I NSCLC die within 10 years after initial diagnosis [2]. Recent studies indicate that some members of the tripartite motif (TRIM) protein family function as important regulators of carcinogenesis [6]. Several studies have reported that TRIM44 contributes to diverse pathological conditions such as cancer, developmental disorders, neurodegenerative diseases, and viral infections [7,8,9,10,11,12,13,14,15,16,17,18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
