TUBB3 Is Associated with High-Grade Histology, Poor Prognosis, p53 Expression, and Cancer Stem Cell Markers in Clear Cell Renal Cell Carcinoma

Sekino, Yohei; Han, Xiangrui; Babasaki, Takashi; Miyamoto, Shunsuke; Kohno, Hiroyuki; Kobayashi, Go; Goto, Keisuke; Inoue, Shogo; Hayashi, Tetsutaro; Teishima, Jun; Sakamoto, Naoya; Sentani, Kazuhiro; Oue, Naohide; Yasui, Wataru; Matsubara, Akio

doi:10.1159/000506775

Cited by 16 publications

(22 citation statements)

References 48 publications

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“…TUBB3 belongs to the family of tubulin proteins being part of microtubules and has been intensively studied as a possible predictor of the efficacy of antitumor agents from the taxane group [1][2][3][4][5]. The uniqueness of TUBB3 as a potential tumor-associated marker is that it is practically not detected in normal epithelial cells [6] and is expressed only at low intensity in endotheliocytes and macrophages [7].…”

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confidence: 99%

Experimental Verification on the Hypothesis about the Possibility of Molecular Diagnostics of Local Tumor Spread on the Lewis Lung Carcinoma Model

Богуш

Maiak

Сапрыкина

et al. 2021

Moscow Univ. Chem. Bull.

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Expression of tumor-associated protein beta-III tubulin (TUBB3) was evaluated quantitatively by immunofluorescence analysis using flow cytometry in lung tissue of intact animals and on day 11 after the Lewis lung carcinoma transplantation as well in lung metastasis tissue and in visually “normal” surrounding tissue. It was shown that the tumor is characterized by a high TUBB3 expression, while also the expression of the marker was detected in both variants of visually normal lung tissue: it was lower than in tumor tissue but significantly higher than in lung tissue of intact animals. The detection of TUBB3 outside the tumor indicates that the tissue appeared to be normal has already involved in malignancy and this supports the hypothesis that tumor-associated protein TUBB3 can be used as a molecular marker of local tumor spread.

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confidence: 99%

Experimental Verification on the Hypothesis about the Possibility of Molecular Diagnostics of Local Tumor Spread on the Lewis Lung Carcinoma Model

Богуш

Maiak

Сапрыкина

et al. 2021

Moscow Univ. Chem. Bull.

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“…But the Kaplan-Meier survival analysis suggested functional cooperation of these two proteins in the aggressiveness of the disease as the high expression of both these proteins or increased expression of even one of these proteins can significantly lead to poor prognosis. It is worthwhile to mention here that, like TUBB4B, its close relatives TUBB2 and TUBB3 have been shown to predict poor survival, the former regulating the cancer energetics through VDAC and the latter by imparting resistance to microtubule targeting agents ( 24 , 38 – 41 ). Our results show that the mechanism by which TUBB4B influences survival is through another means, possibly by regulating the proper localization of Ephrin-B1 in the CSC niche.…”

Section: Discussionmentioning

confidence: 98%

“…Consistent with the overexpression of specific isotypes of tubulins in cancers, the success of several microtubule-targeting agents have been compromised ( 34 – 37 ). Overexpression of both βII tubulin and βIII tubulin are reported in cancer ( 24 , 38 ). βII tubulin is shown to regulate Voltage-Dependent Anion Channels (VDACs) in the mitochondrial outer membrane, which act as a critical regulator of the Warburg effect observed in cancer cells ( 39 , 40 ).…”

Section: Discussionmentioning

confidence: 99%

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β-Tubulin Isotype, TUBB4B, Regulates The Maintenance of Cancer Stem Cells

et al. 2021

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Recent advancements in cancer research have shown that cancer stem cell (CSC) niche is a crucial factor modulating tumor progression and treatment outcomes. It sustains CSCs by orchestrated regulation of several cytokines, growth factors, and signaling pathways. Although the features defining adult stem cell niches are well-explored, the CSC niche is poorly characterized. Since membrane trafficking proteins have been shown to be essential for the localization of critical proteins supporting CSCs, we investigated the role of TUBB4B, a probable membrane trafficking protein that was found to be overexpressed in the membranes of stem cell enriched cultures, in sustaining CSCs in oral cancer. Here, we show that the knockdown of TUBB4B downregulates the expression of pluripotency markers, depletes ALDH1A1+ population, decreases in vitro sphere formation, and diminishes the tumor initiation potential in vivo. As TUBB4B is not known to have any role in transcriptional regulation nor cell signaling, we suspected that its membrane trafficking function plays a role in constituting a CSC niche. The pattern of its expression in tissue sections, forming a gradient in and around the CSCs, reinforced the notion. Later, we explored its possible cooperation with a signaling protein, Ephrin-B1, the abrogation of which reduces the self-renewal of oral cancer stem cells. Expression and survival analyses based on the TCGA dataset of head and neck squamous cell carcinoma (HNSCC) samples indicated that the functional cooperation of TUBB4 and EFNB1 results in a poor prognosis. We also show that TUBB4B and Ephrin-B1 cohabit in the CSC niche. Moreover, depletion of TUBB4B downregulates the membrane expression of Ephrin-B1 and reduces the CSC population. Our results imply that the dynamics of TUBB4B is decisive for the surface localization of proteins, like Ephrin-B1, that sustain CSCs by their concerted signaling.

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“…To knock out p53 in RT4 and RT112 cells, we used CRISPR-Cas9 technology, which was performed as described previously [ 28 ]. p53 single-guide RNAs (sgRNAs; CRISPR-P53 vector) and scrambled sgRNAs (empty vector) were purchased from ABM Inc. (Richmond, BC, Canada).…”

Section: Methodsmentioning

confidence: 99%

KIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer

Sekino

Pham

Kobatake

et al. 2021

JCM

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Kinesin family member C1 (KIFC1), a minus end-directed motor protein, is reported to play an essential role in cancer. This study aimed to analyze KIFC1 expression and examine KIFC1 involvement in cisplatin resistance in bladder cancer (BC). Immunohistochemistry showed that 37 of 78 (47.4%) BC cases were positive for KIFC1. KIFC1-positive cases were associated with high T stage and lymph node metastasis. Kaplan-Meier analysis showed that KIFC1-positive cases were associated with poor prognosis, consistent with the results from public databases. Molecular classification in several public databases indicated that KIFC1 expression was increased in basal type BC. Immunohistochemistry showed that KIFC1-positive cases were associated with basal markers 34βE12, CK5 and CD44. KIFC1 expression was increased in altered TP53 compared to that in wild-type TP53. Immunohistochemistry showed that KIFC1-positive cases were associated with p53-positive cases. P53 knockout by CRISPR-Cas9 induced KIFC1 expression in BC cell lines. Knockdown of KIFC1 by siRNA increased the sensitivity to cisplatin in BC cells. Kaplan-Meier analysis indicated that prognosis was poor among KIFC1-positive BC patients treated with cisplatin-based chemotherapy. Immunohistochemistry showed that KIFC1-positive cases were associated with PD-L1-positive cases. High KIFC1 expression was associated with a favorable prognosis in patients treated with atezolizumab from the IMvigor 210 study. These results suggest that KIFC1 might be a promising biomarker and therapeutic target in BC.

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TUBB3 Is Associated with High-Grade Histology, Poor Prognosis, p53 Expression, and Cancer Stem Cell Markers in Clear Cell Renal Cell Carcinoma

Cited by 16 publications

References 48 publications

Experimental Verification on the Hypothesis about the Possibility of Molecular Diagnostics of Local Tumor Spread on the Lewis Lung Carcinoma Model

Experimental Verification on the Hypothesis about the Possibility of Molecular Diagnostics of Local Tumor Spread on the Lewis Lung Carcinoma Model

β-Tubulin Isotype, TUBB4B, Regulates The Maintenance of Cancer Stem Cells

KIFC1 Is Associated with Basal Type, Cisplatin Resistance, PD-L1 Expression and Poor Prognosis in Bladder Cancer

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