Dynein Light Chain Protein Tctex1: A Novel Prognostic Marker and Molecular Mediator in Glioblastoma

Abstract

The purpose of this study was to determine the role of Tctex1 (DYNLT1, dynein light chain-1) in the pathophysiology of glioblastoma (GBM). To this end, we performed immunohistochemical analyses on tissues from GBM patients (n = 202). Tctex1 was additionally overexpressed in two different GBM cell lines, which were then evaluated in regard to their proliferative and invasive properties. We found that Tctex1 levels were significantly higher in GBM compared to healthy adjacent brain tissues. Furthermore, high Tctex1 expression was significantly associated with the short overall- (p = 0.002, log-rank) and progression-free (p = 0.028, log-rank) survival of GBM patients and was an independent predictor of poor overall survival in multivariate Cox-regression models. In vitro, Tctex1 promoted the metabolic activity, anchorage-independent growth and proliferation of GBM cells. This phenomenon was previously shown to occur via the phosphorylation of retinoblastoma protein (phospho-RB). Here, we found a direct and significant correlation between the levels of Tctex1 and phospho-RB (Ser807/801) in tissues from GBM patients (p = 0.007, Rho = 0.284, Spearman’s rank). Finally, Tctex1 enhanced the invasiveness of GBM cells and the release of pro-invasive matrix metalloprotease 2 (MMP2). These findings indicate that Tctex1 promotes GBM progression and therefore might be a useful therapeutic target in this type of cancer.

Identification of DYNLT1 associated with proliferation, relapse, and metastasis in breast cancer

“…With the development of modern genomic/transcriptomic technologies and increasing public cancer genomic programs, such as TCGA and GEO, numerous biomarkers were identified for improving our ability to diagnose and treat cancer or utilized as predictors of prognosis and response to therapies in cancer. For example, DYNLT1 serving as a prognostic indicator for GBM patients has been reported ( 12 ). However, there is no report on whether DYNLT1 may act as a biomarker of BC.…”

“…It is reported that DYNLT1 plays an important role in many biological functions and diseases, such as Huntington's disease ( 8 ), fertilizing potential of human spermatozoa ( 9 ), migration of epidermal cells in hypoxia ( 10 ), autophagy lysosomal degradation ( 11 ), and several types of cancer. DYNLT1 has been reported to promote glioblastoma progression and is associated with tumor-node-metastasis (TNM) grade ( 12 ). In gastric cancer (GC), DYNLT1 takes part in the miR-15b-3p/Caspase-3/Caspase-9 signaling pathway to promote malignant transformation ( 13 ).…”

PLOD2 Is a Prognostic Marker in Glioblastoma That Modulates the Immune Microenvironment and Tumor Progression

“…TMA blocks were built using the Arraymold kit E (Riverton, UT, USA) as previously described [ 54 , 55 ] and cut into 2 µm sections. The sections were incubated with 667 ng/mL PLOD2-specific polyclonal antibodies (Proteintech Europe, Manchester, UK) or 500 ng/mL anti-human CD66b antibodies (BioLegend, San Diego, CA, USA) at 4 °C overnight.…”

Progesterone Receptor Membrane Component 1 (PGRMC1) Modulates Tumour Progression, the Immune Microenvironment and the Response to Therapy in Glioblastoma

“…TMAs were constructed and stained as previously described [22,23]. The following primary antibodies were used: 112 ng/mL monoclonal rabbit anti-PGRMC1 (Cell Signaling Technology, Frankfurt am Main, Germany), 3.6 µg/mL polyclonal rabbit anti-Integrin beta-1 (Proteintech Europe, Manchester, UK), and 0.66 µg/mL monoclonal mouse anti-CD66b (BioLegend, San Diego, CA, USA).…”