UBAP2Lis amplified in a large subset of human lung adenocarcinoma and is critical for epithelial lung cell identity and tumor metastasis

Abstract

The ubiquitin-associated protein 2-like () gene remains poorly studied in human and mouse development. UBAP2L interacts with the Polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (BMI1) and determines the activity of mouse hematopoietic stem cells Here we show that loss of leads to disorganized respiratory epithelium of mutant neonates, which die of respiratory failure. We also show that overexpression leads to epithelial-mesenchymal transition-like phenotype in a non-small cell lung carcinoma (NSCLC) cell line. is amplified in 15% of human primary lung adenocarcinoma specimens. Such patients express higher levels of and show a reduction in survival when compared with those who do not have this gene amplification. Supporting a possible role for in lung tumor progression, NSCLC cells engineered to express low levels of this gene produce much smaller tumors than wild-type control cells. Together, these results suggest that contributes to epithelial lung cell identity in mice and that it plays an important role in human lung adenocarcinoma.-Aucagne, R., Girard, S., Mayotte, N., Lehnertz, B., Lopes-Paciencia, S., Gendron, P., Boucher, G., Chagraoui, J., Sauvageau, G. is amplified in a large subset of human lung adenocarcinoma and is critical for epithelial lung cell identity and tumor metastasis.

Clinical Significance of Ubiquitin-associated Protein 2-like in Patients With Uterine Cervical Cancer

“…According to previous reports, UBAP2L is up-regulated in hepatocellular carcinoma compared with normal tissues, and the prognosis of patients with high UBAP2L expression is significantly poorer than those with low expression (11,12). Moreover, a similar result was also reported in patients with lung adenocarcinoma (13). Therefore, overexpression of UBAP2L is considered to be associated with poor prognosis and to contribute to cancer progression.…”

“…Therefore, UBAP2L function might differ depending on the cell type, and UBAP2L might have additional unknown functions. In addition, differently from other malignancies in the previous reports (9)(10)(11)(12)(13)(14), cervical cancer is caused by HPV, and its oncogene E6 and E7 target key cell-cycle control proteins (6,20). Therefore, further evaluation of the association between UBAP2L and HPV oncogenes would be interesting.…”

“…The ubiquitinproteasome pathway is commonly used for protein degradation in eukaryotes and is considered to be involved in multiple cellular processes (6)(7)(8). In addition, recent studies have confirmed that UBAP2L functions as an oncogene and is associated with various types of cancer, including prostate cancer (9), glioma (10), hepatocellular carcinoma (11,12), lung adenocarcinoma (13), and breast carcinoma (14). Therefore, inhibition of the ubiquitinproteasome system is a promising anticancer strategy, and several proteasome inhibitors have been approved for clinicaI use (15)(16)(17).…”

Molecularly distinct cores coexist inside stress granules

“…Aside from neurodegeneration, a number of publications show a role of UBAP2L in cancer. UBAP2L appears to act in different malignances as an oncogene, whose expression is required for survival (Chai et al, 2016), growth (He et al, 2018; Li and Huang, 2014; Li et al, 2018; Zhao et al, 2015), and metastasization (Aucagne et al, 2017; Li and Huang, 2014; Li et al, 2018; Ye et al, 2017). Stress granules are often present in cancer cells (reviewed in Mahboubi and Stochaj, 2017), where they may promote cell survival in the stressful condition of the cancer microenvironment (Adjibade et al, 2015; Somasekharan et al, 2015; Vilas-Boas et al, 2016) and metastasization (Somasekharan et al, 2015).…”

“…The relative stability of stress granule cores has recently allowed their purification and the identification of novel stress granule nucleators, among them the protein UBAP2L (Ubiquitin-associated protein 2-like (Markmiller et al, 2018; Youn et al, 2018). UBAP2L is a ubiquitous and abundant protein in human tissues (Beck et al, 2011; Lonsdale et al, 2013; Melé et al, 2015; Uhlén et al, 2015), it promotes cancer progression and metastasis (Aucagne et al, 2017; Chai et al, 2016; He et al, 2018; Li and Huang, 2014; Li et al, 2018; Ye et al, 2017, P. 20; Zhao et al, 2015) and may be involved in neurodegenerative diseases (Markmiller et al, 2018). Despite its abundance and potential implication in diseases, the exact role of UBAP2L in cell physiology and stress granule formation is not yet understood.…”