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Background
Class III β-tubulin (βIII-tubulin) has been reported to express at the invasive margin of colorectal cancer. The present study aimed to investigate the clinical implication of βIII-tubulin expression at the invasive margin of colorectal cancer.
Material/Methods
We recruited 111 patients with surgically resected colorectal carcinoma for...
Context in source publication
Context 1
... other data (age, sex, lymphatic metastasis, TNM stage, local recurrence, distant metastasis, and mortality) were not found to be significantly associated with positive staining of bIII-tubulin. There was no significant difference in the clinical data among the groups with different bIII-tubulin staining in- tensity (Table 3) Tissue distribution of bIII-tubulin in colorectal carcinoma patients ...
Citations
... In colorectal cancer, elevated TUBB3 expression is associated with invasive phenotypes in both genders (Portyanko et al., 2009;Zhao et al., 2016). In vitro analysis of 23 colorectal cancer cell lines suggested that TUBB3/βIIItubulin is activated after exposure to androgens in males , as seen with estrogens in breast cancer cells (Saussede-Aim et al., 2009a). ...
Microtubule proteins form a dynamic component of the cytoskeleton, and play key roles in cellular processes, such as vesicular transport, cell motility and mitosis. Expression of microtubule proteins are often dysregulated in cancer. In particular, the microtubule protein βIII-tubulin, encoded by the TUBB3 gene, is aberrantly expressed in a range of epithelial tumours and is associated with drug resistance and aggressive disease. In normal cells, TUBB3 expression is tightly restricted, and is found almost exclusively in neuronal and testicular tissues. Understanding the mechanisms that control TUBB3 expression, both in cancer, mature and developing tissues will help to unravel the basic biology of the protein, its role in cancer, and may ultimately lead to the development of new therapeutic approaches to target this protein. This review is devoted to the transcriptional and posttranscriptional regulation of TUBB3 in normal and cancerous tissue.
... To date, the relationship between TUBB3 and prognosis is not well defined. TUBB3 expression has been considered a predictor of tumor progression and aggressive behavior regardless of therapeutic options in various tumors [22][23][24][25][26][27][28]; however, other studies reported that high TUBB3 expression was associated with a superior response to drugs [42][43][44][45]. These findings indicate that TUBB3 expression might be regulated in a complicated pattern and influenced by various biological factors or microenvironments. ...
Although American Thyroid Association guidelines offer a risk stratification scheme for thyroid cancer patients, there is a continuous need for more sophisticated biomarkers that can predict disease progression. In this study, we aim to evaluate the prognostic value of class III beta-tubulin (TUBB3) and uncover the relationship between TUBB3 and invasive potential in thyroid carcinoma. Immunohistochemistry (IHC) for TUBB3 and E-cadherin was performed on a total of 254 cases of thyroid cancer specimens. Tumor budding at the invasive margin was evaluated. In vitro functional studies were also performed; the protein and mRNA levels of TUBB3 were compared among the five cell types at baseline, with transwell invasion and after blocking of TUBB3 by shRNA. IHC revealed that the levels of TUBB3 were higher in conventional papillary carcinomas (cPTCs) and anaplastic thyroid carcinomas (ATCs). In univariate analysis, high tumor budding and TUBB3 expression were associated with inferior progression-free survival in cPTC. The results of a Western blot and RT-PCR agreed with the IHC finding. The results were further validated through data from The Cancer Genome Atlas database. Our results suggest that high expression of TUBB3 in thyroid carcinoma could predict invasive potential and possibly be linked with epithelial–mesenchymal transition.
... Our study was focused on normal colon samples and colonic neoplasms. (29). In some studies, researchers claimed that TUBB3 was expressed at the invasive edges of neoplasms (28,29). ...
... (29). In some studies, researchers claimed that TUBB3 was expressed at the invasive edges of neoplasms (28,29). In our study, the non-invasive colon adenomas had a varying range of TUBB3 expression. ...
Background/Aim: The challenges of cololorectal cancer (CRC) management include prediction of outcome and drug response or chemoresistance. This study aimed at examining whether βIII-tubulin (TUBB3), present in various types of normal tissues and cancer, is a biomarker for the response of colorectal neoplasms to paclitaxel. Materials and Methods: Six tissue microarrays (TMAs) including 14 colon mucosa, 78 polyps and 202 CRCs were constructed. Assessment of TUBB3 expression was performed by immunohistochemistry, and it was scored as negative, focal and positive. In the HCT116 cell line, TUBB3 expression was silenced with siRNA. Paclitaxel toxicity was evaluated in TUBB3-silenced and control HCT116 cell lines. Results: The non-neoplastic colon mucosa was negative for TUBB3, while some of colon adenomas and CRCs expressed TUBB3 in various levels from focal to diffuse. TUBB3-expressing CRCs tended to have poor prognosis and silencing of TUBB3 sensitized the cells to paclitaxel. Conclusion: TUBB3 was expressed in a subgroup of colorectal neoplasms. Suppression of TUBB3 potentialy sensitizes neoplastic cells to taxanes. © International Institute of Anticancer Research. All rights reserved.
... An up-regulation of the protein Ezrin has been shown in the sentinel lymph nodes of colorectal cancer [35]. Similarly, changes in class III and V beta-Tubulin was reported to closely relate with CRC [36,37]. In addition, the identified down-regulated proteins ARPC3, ARPC5, clathrin heavy chain 1 (CLTC), ITGB1, and VCL are involved with bacterial invasion of epithelial cells, while ITGB1 and VCL are also related to the process of leukocyte transendothelial migration. ...
Background
The molecular mechanisms or valuable biomarkers for early diagnosis of colorectal cancer (CRC) are not fully elucidated yet.
Objective
To understand the proteomic changes at the global level in the carcinogenesis of CRC, differentially expressed proteins between normal intestinal epithelial cells CCD841 and colorectal cancer cells HCT116 were identified.
Method
The isobaric tags for relative and absolute quantitation (iTRAQ) coupled with 2D LC-MS/MS proteomic approach were performed for screening the altered proteins between cells CCD841 and HCT116.
Results
A total of 1947 proteins were identified after filtering and using a 1% false discovery rate. Based on a final cutoff (> 3.16 and < 0.32), 229 proteins were found to be significantly altered, among which 95 (41%) were up-regulated while 134 (59%) were down-regulated. Gene Ontology analysis revealed that the differentially expressed proteins were mainly cell part proteins involved in cellular process and binding in terms of subcellular distribution, biological process, and molecular function. KEGG analysis indicated that the differentially expressed proteins were significantly involved in the process of focal adhesion, pathogenic Escherichia coli infection, leukocyte transendothelial migration, bacterial invasion of epithelial cells, regulation of actin cytoskeleton, DNA replication and so on.
Conclusion
Collectively, our data identified differentially expressed proteins in colon cancer carcinogenesis, which could provide the clues on unraveling the molecular mechanism of CRC.
... the β-tubulin in the different CRCs cell lines on pillars (fig 4.10 and 4.11)[350][351][352][353] . On the other hand, e-cadherins are type of cell adhesion molecules (CAM) whose loss is known to promote metastasis of cancer cells. ...
This thesis deals with understanding behaviour of different cancer cell types on microstructured topography. We studied the behaviour of osteosarcoma cell line (SaOS-2) on confined micropillar structures and in particular their nuclear deformation. We analysed the role of the cytoskeleton, focal adhesions (FAs), nucleoskeleton (LINC and lamin A) and chromatin in SaOS-2 deformation on micropillar topography. Actomyosin and vimentin intermediate filament were shown to play a crucial role in orchestrating nuclear deformation. We found that FAs arrangement was mostly on side walls of pillars and that the LINC-cytoskeletal connection was essential for the nuclear deformation process but not lamin A. Employing chemo-topography modulations of pillars and a computational simulation model we demonstrated that the pulling down forces and not pushing down forces drive the cellular-nuclear deformation in osteosarcoma cells. We also studied the nuclear deformation of SaOS-2 on hydrogel micropillars with different stiffness and chemistry. We saw that cell morphology, actin organization and FAs behaviour was modulated by the substrate mechanics and chemistry. To explore the role of cancer origin, we examined the behaviour of various colon carcinomas on various micro-topographies and found that the epithelial origin cancers are less responsive to microscale topography compared to mesenchymal origin cancerous cells. However, their behaviour was affected on large pits which resembled the intestinal crypt and villi arrangement in terms of size.
... Overexpression of TUBB3 in colorectal carcinoma, identified in tumour invasion margins [17,22,56], is correlated to the degree of tumour differentiation, lymphatic metastasis [85], poorer prognostic and lower overall survival [44]. Not at last, TUBB3 expression, 4.1 times higher in the uterine serous carcinomas compared to the ovarian serous ones, pleads for its prognostic value [15,64]. ...
The present study aims to analyse the expression of class III β-tubulin (TUBB3) in different histological subtypes of papillary thyroid carcinoma (PTC), its relationship with the clinico-pathological factors and the potential prognostic role in the risk stratification and therapy. We evaluated the immunohistochemical TUBB3 expression in 70 cases of sporadic PTC divided in low-and high-risk subgroups based on histological criteria. We demonstrated a significant correlation between TUBB3 expression (low and moderate versus high) and the risk subgroups and tumour relapse, respectively. No association was found between TUBB3 expression and age, gender, tumour size, tumour focality, lympho-vascular invasion, extrathyroidal extension, lymph node metastases and tumour stage. Our results sustain the potential of TUBB3 as marker for prognostic stratification. Consequently, the therapy with taxanes, anti-microtubule agents that inhibit mitosis by disrupting microtubules, could be considered in the aggressive PTC cases that need a personalized therapy. © 2018, Romanian Society for Pharmaceutical Sciences. All rights reserved.
... Approximately 5-10% of CRC cases are due to familial adenomatous polyposis, which is caused by inherited mutations in the tumor suppressor gene APC (about 1% of all CRC cases) (Half et al., 2009). Nonfamilial CRCs are more common (≈ two third of the cases) and are frequently associated with alterations in several molecular pathways, including over-activation of the epidermal growth factor receptor (EGFR) (Markman et al., 2010;Yarom and Jonker, 2011), alterations in the embryonic development pathways (Wnt/β-catenin-EMT) (Bates and Mercurio, 2005;Bertrand et al., 2012), inhibition of apoptotic signaling pathways (Bedi et al., 1995;Watson, 2004;Zhang and Yu, 2013), and dysregulation of microtubule dynamics (Carles et al., 1999;Giarnieri et al., 2005;Zhao et al., 2016). ...
The inhibition of apoptosis, disruption of cellular microtubule dynamics, and over-activation of the epithelial mesenchymal transition (EMT), are involved in the progression, metastasis, and resistance of colorectal cancer (CRC) to chemotherapy. Therefore, the design of a molecule that can target these pathways could be an effective strategy to reverse CRC progression and metastasis. In this study, twelve novel silybin derivatives, HM015a-HM015k (15a−15k) and compound 17, were screened for cytotoxicity in CRC cell lines. Compounds HM015j and HM015k (15k and 15j) significantly decreased cell proliferation, inhibited colony formation, and produced cell cycle arrest in CRC cells. Furthermore, 15k significantly induced the formation of reactive oxygen species and apoptosis. It induced the cleavage of the intrinsic apoptotic protein (Bax p21) to its more efficacious fragment, p18. Compound 15k also inhibited tubulin expression and disrupted its structure. Compound 15k significantly decreased metastatic LOVO cell migration and invasion. Furthermore, 15k reversed mesenchymal morphology in HCT116 and LOVO cells. Additionally, 15k significantly inhibited the expression of the mesenchymal marker N-cadherin and upregulated the expression of the epithelial marker, E-cadherin. Compound 15k inhibited the expression of key proteins known to induce EMT (i.e., DVL3, β-catenin, c-Myc) and upregulated the anti-metastatic protein, cyclin B1. Overall, in vitro, 15k significantly inhibited CRC progression and metastasis by inhibiting apoptosis, tubulin activity and the EMT pathways. Overall, these data suggest that compound 15k should be tested in vivo in a CRC animal model for further development.
... BRAF was preferentially mutated in RSCC, and EGFR (epidermal growth factor receptor) was prevalently amplified in LCRC3. Class III betatubulin (β-Tubulin III) had been reported to express at the invasive margin of CRC, and its expression level was correlated with tumor differentiation and lymphatic metastasis [25] . The mutation incidence of p53 gene was reported to be as high as 42.4% in CRC [26] . ...
... BRAF was preferentially mutated in RSCC, and EGFR (epidermal growth factor receptor) was prevalently amplified in LCRC 3 . Class III beta-tubulin (β-Tubulin III) had been reported to express at the invasive margin of CRC, and its expression level was correlated with tumor differentiation and lymphatic metastasis 25 . The mutation incidence of p53 gene was reported to be as high as 42.4% in CRC 26 . ...
To compare protein expression levels, gene mutation and survival among Right-Sided Colon Cancer (RSCC), Left-Sided Colon Cancer (LSCC) and rectal cancer patients, 57 cases of RSCC, 87 LSCC and 145 rectal cancer patients were included retrospectively. Our results demonstrated significant differences existed among RSCC, LSCC and rectal cancer regarding tumor diameter, differentiation, invasion depth and TNM stage. No significant difference was identified in expression levels of MLH1, MSH2, MSH6, PMS2, β-Tubulin III, P53, Ki67 and TOPIIα, and gene mutation of KRAS and BRAF among three groups. Progression Free Survival (PFS) of RSCC was significantly lower than that of LRCC and rectal cancer. In univariate analyses, RSCC, preoperative chemoradiotherapy, poor differentiation, advanced TNM stage, elevated serum CEA and CA19-9 level, tumor deposit, perineural and vascular invasion were found to be predictive factors of shorter PFS. In multivariate analyses, only differentiation and TNM stages were found to be independent predictors of PFS. In conclusion, compared with LSCC and rectal cancer, RSCC has larger tumor size, poor differentiation, advanced TNM stage and shorter survival. The shorter survival in RSCC might be attributed to the advanced tumor stage caused by its inherent position feature of proximal colon rather than genetic difference.
... Research conducted over the past decade has indicated several tubulin isotypes as potential prognostic markers whose expression levels in primary tumours are associated with aggressive disease with greater metastatic potential and the propensity of patients to suffer metastatic relapse, although the major focus has centred on βIII-tubulin expression. In particular, clinical data has identified that high βIII-tubulin protein expression strongly correlates with aggressive clinical behaviour and poor patient outcome in many forms of cancer, including breast, ovarian, gastric, glioblastoma, prostate, colorectal, pancreatic and NSCLC [39,47,66,121,132,[207][208][209][210][211][212][213]. βIII-Tubulin expression is associated with high-grade malignancy in gliomas and gastric cancers [47,132,208,209,214,215]. ...
... High βIII-tubulin expression is also detected at the invasive tumour edge of atypical carcinoid lung cancers [211], in lymph node metastases from primary adenocarcinoma NSCLC [216] and in metastatic lung cancers derived from colon, prostate and ovarian tumours but not from primary tumours of the breast [211]. In colorectal cancer, the expression of βIII-tubulin expression also correlates with high grade malignancy, tumour differentiation and lymphatic metastasis, suggesting a potential role of βIII-tubulin in prostate tumour differentiation and metastasis [213]. Overexpression of βIII-tubulin is observed in breast cancer brain metastases and its expression is significantly associated with distant metastases [121]. ...
Tubulin proteins, as components of the microtubule cytoskeleton perform critical cellular functions throughout all phases of the cell cycle. Altered tubulin isotype composition of microtubules is emerging as a feature of aggressive and treatment refractory cancers. Emerging evidence highlighting a role for tubulin isotypes in differentially influencing microtubule behaviour and broader functional networks within cells is illuminating a complex role for tubulin isotypes regulating cancer biology and chemotherapy resistance. This review focuses on the role of different tubulin isotypes in microtubule dynamics as well as in oncogenic changes that provide a survival or proliferative advantage to cancer cells within the tumour microenvironment and during metastatic processes. Consideration of the role of tubulin isotypes beyond their structural function will be essential to improving the current clinical use of tubulin-targeted chemotherapy agents and informing the development of more effective cancer therapies.
