TUBB3 Promotes Growth and Invasion of Gallbladder Cancer Cells by Akt/mTOR Signal Pathway

Liu, Zijun; Li, Suqin; Dong, Jiahao; Miao, Yi

doi:10.1615/jenvironpatholtoxicoloncol.2021036821

Cited by 9 publications

(6 citation statements)

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“…We demonstrated that TUBB3 expression was associated with a high Ki-67 labeling index in the UTUC and BLCA-TCGA data, consistent with previous studies showing an association between TUBB3 and cell proliferation in several cancers. 18,19,23 In fact, we previously demonstrated the functional role of TUBB3 in significantly increased cell proliferative ability in TUBB3 siRNA-transfected ccRCC cells. 18 These findings suggest the potential utility of TUBB3 as a proliferation marker in UC.…”

Section: Discussionmentioning

confidence: 91%

Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology

Kobayashi,

Hayashi,

Sentani

et al. 2023

Pathology International

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AbstractβIII‐Tubulin, encoded by the TUBB3 gene, is a microtubule protein. We previously reported that TUBB3 is overexpressed in renal cell carcinoma. We investigated the clinicopathological significance of TUBB3 in upper tract urothelial carcinoma (UTUC) by immunohistochemistry. In normal tissue, TUBB3 expression was weak or absent. In contrast, TUBB3 overexpression was observed in urothelial carcinoma (UC) tissues in 51 (49%) of 103 UTUC cases. TUBB3 overexpression was associated with nodular/flat morphology, high‐grade disease, high T stage, and a poor prognosis. Similar results were obtained in The Cancer Genome Atlas bladder cancer cohort. TUBB3 expression was also associated with high Ki‐67 labeling index, CD44v9, HER2, EGFR, and p53 expression in UTUC. Among representative cancer‐related molecules, TUBB3 was an independent predictor of progression‐free survival and high‐grade UC. Finally, using urine cytology samples, we analyzed TUBB3 expression by immunocytochemistry. TUBB3 expression was more frequently found in UC cells than in nonneoplastic cells. The diagnostic accuracy of urine cytology was improved when combined with TUBB3 immunostaining. The findings suggest the importance of TUBB3 in tumor progression and its potential application as a biomarker for high‐grade disease and the prognosis of UC. Moreover, combination with TUBB3 immunostaining might improve the diagnostic accuracy of urine cytology.

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Section: Discussionmentioning

confidence: 91%

Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology

Kobayashi,

Hayashi,

Sentani

et al. 2023

Pathology International

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“…Furthermore, IL-6 plays a role in safeguarding cancer cells against DNA damage, oxidative stress, and apoptosis caused by treatment, which is achieved by promoting repair and the induction of an anti-signaling mechanism [ 31 , 32 ]. Abnormal expression of β-tubulin-III (TUBB3) is associated with aggressive tumor characteristics and adverse clinical outcomes, significant overexpression of TUBB3 in gallbladder cancer samples and cell lines, reduced overall survival due to high TUBB3 levels, and can also induce the development of gallbladder cancer through the Akt/mTOR signaling pathway, thus becoming a potential target for gallbladder cancer treatment [33] . Collagen type 13 alpha 1 (COL13A1) collagen supports important carcinogenic properties of tumor invasion, and in bladder cancer (BCA), COL13A1 levels are significantly increased, which can be a potential diagnostic and prognostic biomarker for BCA [34] .…”

Section: Discussionmentioning

confidence: 99%

Anoikis-related gene CDKN2A predicts prognosis and immune response and mediates proliferation and migration in thyroid carcinoma

Tang,

Luo,

Zhou

et al. 2024

Translational Oncology

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“…Mutations in TUBB3 were previously reported in facial palsy and peripheral neuropathy [ 32 ] and also reported in the development of gallbladder cancers through Akt/mTOR signal pathway [ 27 ]. Other than 6TI, repeated PPIs of γ -tubulin subtypes (TUBGCP2, TUBGCP3, TUBGCP4, and TUBGCP5) were observed, and such involvement of γ -tubulins subtypes was previously reported to play essential role in GCP formation during assembly of microtubules.…”

Section: Discussionmentioning

confidence: 99%

“…The association of tubulin isotypes with non-tubulin proteins was largely dependent on various signaling pathways and posttranslational modifications of tubulins such as acetylation, phosphorylation, tyrosination, polyglutamylation, and methylation [ 27 , 37 , 46 , 47 ]. The acetylation and phosphorylation of β-tubulin in reducing microtubule assembly were previously reported, and enzymes like minikinase/DYRK1a or cyclin-dependent kinase Cdk1 were involved in such processes [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Prediction of anti-microtubular target proteins of tubulins and their interacting proteins using Gene Ontology tools

Babu

2023

Journal of Genetic Engineering and Biotechnology

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Background Tubulins are highly conserved globular proteins involved in stabilization of cellular cytoskeletal microtubules during cell cycle. Different isoforms of tubulins are differentially expressed in various cell types, and their protein–protein interactions (PPIs) analysis will help in identifying the anti-microtubular drug targets for cancer and neurological disorders. Numerous web-based PPIs analysis methods are recently being used, and in this paper, I used Gene Ontology (GO) tools, e.g., Stringbase, ProteomeHD, GeneMANIA, and ShinyGO, to identify anti-microtubular target proteins by selecting strongly interacting proteins of tubulins. Results I used 6 different human tubulin isoforms (two from each of α-, β-, and γ-tubulin) and found several thousands of node-to-node protein interactions (highest 4956 in GeneMANIA) and selected top 10 strongly interacting node-to-node interactions with highest score, which included 7 tubulin family protein and 6 non-tubulin family proteins (total 13). Functional enrichment analysis indicated a significant role of these 13 proteins in nucleation, polymerization or depolymerization of microtubules, membrane tethering and docking, dorsal root ganglion development, mitotic cycle, and cytoskeletal organization. I found γ-tubulins (TUBG1, TUBGCP4, and TUBBGCP6) were known to contribute majorly for tubulin-associated functions followed by α-tubulin (TUBA1A) and β-tubulins (TUBB AND TUBB3). In PPI results, I found several non-tubular proteins interacting with tubulins, and six of them (HTT, DPYSL2, SKI, UNC5C, NINL, and DDX41) were found closely associated with their functions. Conclusions Increasing number of regulatory proteins and subpopulation of tubulin proteins are being reported with poor understanding in their association with microtubule assembly and disassembly. The functional enrichment analysis of tubulin isoforms using recent GO tools resulted in identification of γ-tubulins playing a key role in microtubule functions and observed non-tubulin family of proteins HTT, DPYSL2, SKI, UNC5C, NINL, and DDX41 strongly interacting functional proteins of tubulins. The present study yields a promising model system using GO tools to narrow down tubulin-associated proteins as a drug target in cancer, Alzheimer’s, neurological disorders, etc.

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TUBB3 Promotes Growth and Invasion of Gallbladder Cancer Cells by Akt/mTOR Signal Pathway

Cited by 9 publications

References 0 publications

Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology

Clinicopathological significance of TUBB3 in upper tract urothelial carcinoma and possible application in urine cytology

Anoikis-related gene CDKN2A predicts prognosis and immune response and mediates proliferation and migration in thyroid carcinoma

Prediction of anti-microtubular target proteins of tubulins and their interacting proteins using Gene Ontology tools

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