Overexpression and translocation of dynamin 2 promotes tumor aggressiveness in breast carcinomas

Dynamin 2 is a GTPase protein that has been implicated in cancer progression through its various roles such as endocytosis, morphogenesis, epithelial-mesenchymal transition (EMT), cellular contractions, and focal adhesion maturation. The increased expression levels of this molecule have been demonstrated with the development of several cancers such as prostate, pancreas, and bladder. However, its clinical significance in breast cancer is unclear yet. In the present study, the membranous, cytoplasmic, and nuclear expression levels of dynamin 2 molecule were evaluated for the first time, using immunohistochemistry (IHC) on tissue microarray (TMA) slides in 113 invasive breast cancer tissues. Moreover, afterward, the association between the dynamin 2 expression and clinicopathological features was determined. Our finding showed that, a higher nuclear expression of dynamin 2 is significantly associated with an increase in tumor stage (P = 0.05), histological grade (P = 0.001), and age of the patients (P = 0.03). In addition, analysis of the cytoplasmic expression levels of this molecule revealed that, there was a statistically significant difference between the expression levels of dynamin 2 among the different breast cancer subtypes (P = 0.003). Moreover, a significant association was found between the increased expression of dynamin 2 membranous and vascular invasion (VI) (P = 0.02). We showed that dynamin 2 protein expression has an association with more aggressive tumor behavior and more advanced disease in the patients with breast cancer; therefore, dynamin 2 molecule could be considered as an indicator of disease progression and aggressiveness

Tumor Matrix Stiffness Provides Fertile Soil for Cancer Stem Cells

Matrix stiffness is a mechanical characteristic of the extracellular matrix (ECM) that increases from the tumor core to the tumor periphery in a gradient pattern in a variety of solid tumors and can promote proliferation, invasion, metastasis, drug resistance, and recurrence. Cancer stem cells (CSCs) are a rare subpopulation of tumor cells with self-renewal, asymmetric cell division, and differentiation capabilities. CSCs are thought to be responsible for metastasis, tumor recurrence, chemotherapy resistance, and consequently poor clinical outcomes. Evidence suggests that matrix stiffness can activate receptors and mechanosensor/mechanoregulator proteins such as integrin, FAK, and YAP, modulating the characteristics of tumor cells as well as CSCs through different molecular signaling pathways. A deeper understanding of the effect of matrix stiffness on CSCs characteristics could lead to development of innovative cancer therapies. In this review, we discuss how the stiffness of the ECM is sensed by the cells and how the cells respond to this environmental change as well as the effect of matrix stiffness on CSCs characteristics and also the key malignant processes such as proliferation and EMT. Then, we specifically focus on how increased matrix stiffness affects CSCs in breast, lung, liver, pancreatic, and colorectal cancers. We also discuss how the molecules responsible for increased matrix stiffness and the signaling pathways activated by the enhanced stiffness can be manipulated as a therapeutic strategy for cancer

High expression of Talin-1 is associated with tumor progression and recurrence in melanoma skin cancer patients.

BACKGROUND: Talin-1 as a component of multi-protein adhesion complexes plays a role in tumor formation and migration in various malignancies. This study investigated Talin-1 in protein levels as a potential prognosis biomarker in skin tumors. METHODS: Talin-1 was evaluated in 106 skin cancer (33 melanomas and 73 non-melanomas skin cancer (NMSC)) and 11 normal skin formalin-fixed paraffin-embedded (FFPE) tissue samples using immunohistochemical technique on tissue microarrays (TMAs). The association between the expression of Talin-1 and clinicopathological parameters, as well as survival outcomes, were assessed. RESULTS: Our findings from data minings through bioinformatics tools indicated dysregulation of Talin-1 in mRNA levels for skin cancer samples. In addition, there was a statistically significant difference in Talin-1 expression in terms of intensity of staining, percentage of positive tumor cells, and H-score in melanoma tissues compared to NMSC (P = 0.001, P \u3c 0.001, and P \u3c 0.001, respectively). Moreover, high cytoplasmic expression of Talin-1 was found to be associated with significantly advanced stages (P = 0.024), lymphovascular invasion (P = 0.023), and recurrence (P = 0.006) in melanoma cancer tissues. Our results on NMSC showed a statistically significant association between high intensity of staining and the poor differentiation (P = 0.044). No significant associations were observed between Talin-1 expression levels and survival outcomes of melanoma and NMSC patients. CONCLUSION: Our observations showed that higher expression of Talin1 in protein level may be significantly associated with more aggressive tumor behavior and advanced disease in patients with skin cancer. However, further studies are required to find the mechanism of action of Talin-1 in skin cancers

The Association Between Higher Expression of Talin-1 and the Reduced Survival Rate in Ovarian Serous Carcinoma Patients

Background & Objective: Talin-1 is a constituent of the multiprotein adhesion complexes that play main role in the formation of tumors and migration in different types of malignancies. The present study aimed to assess expression and prognostic significance of the talin-1 protein in ovarian serous carcinoma (OSC) patients. Methods: The expression of talin-1 in mRNA and its protein levels were investigated for ovarian cancer (OC) by using bioinformatics tools, including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Gene Expression Database of Normal and Tumor Tissue 2 (GENT2), and The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) databases. Thereafter, immunohistochemical (IHC) staining was used to study the expression patterns of the talin-1 protein using 46 paraffin-embedded OSC tissue specimens, 25 benign tumors, and 20 normal tissues, which were assembled in tissue microarrays (TMAs). We also assessed the potential association between the expression of the talin-1 protein, various clinicopathological parameters, and survival outcomes. Results: Our IHC examination for talin-1 was significantly overexpressed in OSC tissues compared to benign tumors and normal tissues. The Kaplan-Meier survival analysis has also indicated statistically significant differences in terms of diseasespecific survival (DSS) and progression-free survival (PFS) between the patients with high and low expression levels of talin-1, respectively. Conclusion: The talin-1 protein was overexpressed in OSC tissues, and a high expression level of talin-1 was found to be significantly associated with tumor aggressiveness and poorer DSS or PFS. Therefore, talin-1 may serve as a molecular marker of cancer progression and a novel prognostic biomarker in these patients

Human telomerase reverse transcriptase protein expression predicts tumour aggressiveness and survival in patients with clear cell renal cell carcinoma

Human telomerase reverse transcriptase (hTERT) is an active component of telomerase and responsible for its catalytic activity, associated with cell proliferation and differentiation. For the first time, the present study was conducted to evaluate the expression and prognostic significance of hTERT in different histological subtypes of renal cell carcinoma (RCC). Expression of hTERT was examined in 176 well-defined renal tumour samples including clear cell RCCs (ccRCCs), papillary and chromophobe RCCs using immunohistochemistry on tissue microarrays. The association between hTERT expression and clinicopathological parameters as well as survival outcomes were then analysed. There was a statistically significant difference in terms of hTERT expression among various RCC subtypes. In ccRCC, increased expression of hTERT was significantly associated with advanced stage, higher grade, presence of microvascular invasion, lymph node invasion, and metastasis. Moreover, in the multivariate analysis, tumour stage and tumour size were independent predictors of the disease-specific survival (DSS). Additionally, expression of hTERT was found to be a significant predictor of worse DSS (p = 0.012) in the univariate analysis. In papillary carcinoma samples (type I and II), significant association was detected between hTERT expression and the tumour stage (p = 0.010, p = 0.050), respectively. In chromophobe RCC, no significant association was detected between expression of hTERT and clinicopathological parameters and survival data. We showed that hTERT protein expression was associated with more aggressive tumour behaviour and more advanced disease in ccRCC patients. Also, hTERT may be a novel poor prognostic indicator of DSS, if the patients are followed for more prolonged time periods

Tumor matrix stiffness provides fertile soil for cancer stem cells

Abstract Matrix stiffness is a mechanical characteristic of the extracellular matrix (ECM) that increases from the tumor core to the tumor periphery in a gradient pattern in a variety of solid tumors and can promote proliferation, invasion, metastasis, drug resistance, and recurrence. Cancer stem cells (CSCs) are a rare subpopulation of tumor cells with self-renewal, asymmetric cell division, and differentiation capabilities. CSCs are thought to be responsible for metastasis, tumor recurrence, chemotherapy resistance, and consequently poor clinical outcomes. Evidence suggests that matrix stiffness can activate receptors and mechanosensor/mechanoregulator proteins such as integrin, FAK, and YAP, modulating the characteristics of tumor cells as well as CSCs through different molecular signaling pathways. A deeper understanding of the effect of matrix stiffness on CSCs characteristics could lead to development of innovative cancer therapies. In this review, we discuss how the stiffness of the ECM is sensed by the cells and how the cells respond to this environmental change as well as the effect of matrix stiffness on CSCs characteristics and also the key malignant processes such as proliferation and EMT. Then, we specifically focus on how increased matrix stiffness affects CSCs in breast, lung, liver, pancreatic, and colorectal cancers. We also discuss how the molecules responsible for increased matrix stiffness and the signaling pathways activated by the enhanced stiffness can be manipulated as a therapeutic strategy for cancer

High expression of Talin-1 is associated with tumor progression and recurrence in melanoma skin cancer patients

Abstract Background Talin-1 as a component of multi-protein adhesion complexes plays a role in tumor formation and migration in various malignancies. This study investigated Talin-1 in protein levels as a potential prognosis biomarker in skin tumors. Methods Talin-1 was evaluated in 106 skin cancer (33 melanomas and 73 non-melanomas skin cancer (NMSC)) and 11 normal skin formalin-fixed paraffin-embedded (FFPE) tissue samples using immunohistochemical technique on tissue microarrays (TMAs). The association between the expression of Talin-1 and clinicopathological parameters, as well as survival outcomes, were assessed. Results Our findings from data minings through bioinformatics tools indicated dysregulation of Talin-1 in mRNA levels for skin cancer samples. In addition, there was a statistically significant difference in Talin-1 expression in terms of intensity of staining, percentage of positive tumor cells, and H-score in melanoma tissues compared to NMSC (P = 0.001, P < 0.001, and P < 0.001, respectively). Moreover, high cytoplasmic expression of Talin-1 was found to be associated with significantly advanced stages (P = 0.024), lymphovascular invasion (P = 0.023), and recurrence (P = 0.006) in melanoma cancer tissues. Our results on NMSC showed a statistically significant association between high intensity of staining and the poor differentiation (P = 0.044). No significant associations were observed between Talin-1 expression levels and survival outcomes of melanoma and NMSC patients. Conclusion Our observations showed that higher expression of Talin1 in protein level may be significantly associated with more aggressive tumor behavior and advanced disease in patients with skin cancer. However, further studies are required to find the mechanism of action of Talin-1 in skin cancers

Co-expression of cancer stem cell markers, SALL4/ALDH1A1, is associated with tumor aggressiveness and poor survival in patients with serous ovarian carcinoma

Abstract Background Spalt-like transcription factor 4 (SALL4) and aldehyde dehydrogenase1 family member A1 (ALDH1A1) expressing cells have been characterized as possessing stem cell-like properties known as cancer stem cell marker in serous ovarian carcinoma (SOC). Methods The association between SALL4 and ALDH1A1 was observed based on literature review and bioinformatics tools. Therefore, this study aimed to investigate the association between the co-expression of SALL4/ALDH1A1 proteins and clinicopathological parameters and their prognostic value in SOC patients using immunohistochemical staining on tissue microarrays (TMAs). Furthermore, benign tumors and normal tissue samples were compared with the expression of the tumor tissue samples. Results Increased co-expression of SALL4/ALDH1A1 was found to be significantly associated with the advanced FIGO stage (P = 0.047), and distant metastasis (P = 0.028). The results of Kaplan–Meier survival analysis indicated significant differences between disease- specific survival (DSS; P = 0.034) or progression-free survival (PFS; P = 0.018) and the patients with high and low co-expression of SALL4/ALDH1A1, respectively. Furthermore, high level co-expression of SALL4/ALDH1A1 was a significant predictor of worse DSS and PFS in the univariate analysis. The data also indicated that the co-expression of SALL4/ALDH1A1 was an independent prognostic factor affecting PFS. Moreover, the co-expression of SALL4/ALDH1A1 added prognostic values of DSS in patients with SOC who had grade III versus grade I in multivariate analysis. Conclusions Our data demonstrated that high co-expression of SALL4/ALDH1A1 was found to be significantly associated with tumor aggressiveness and worse DSS or PFS in SOC patients. Therefore, co-expression of SALL4/ALDH1A1 may serve as a potential prognostic biomarker of cancer progression in these cases