TrkB promotes laryngeal cancer metastasis via activation PI3K/AKT pathway

Jiang, Liang; Wang, Zhihai; Liu, Chuan; Gong, Zhongying; Yang, Yucheng; Kang, Hou‐Yong; Li, Yanshi; Hu, Guohua

doi:10.18632/oncotarget.21711

Cited by 21 publications

(18 citation statements)

References 37 publications

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“…On the other hand, the Akt inhibitor effectively blocked TGFβ1-induced oral cancer cell migration. Previous studies reported that Akt activates Twist, a basic helix-loop-helix transcription factor by phosphorylating the Ser16 residue, which induces EMT in HNSCC [32][33][34]. Although, in this study SMAD2/3 and MAPK were also phosphorylated in TGFβ1-induced oral cancer cells results indicated that these signalling molecules were not involved in cell migration.…”

Section: Discussioncontrasting

confidence: 64%

Is it all just an Akt - you’d be SMAD to believe it! Role of TGFβ1 in oral cancer metastasis

Alghamdi¹,

Shalgm²,

Ellis³

et al. 2018

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Introduction: TGFβ1 activates both SMAD and non-SMAD dependent signalling pathways but their role in oral cancer cell migration and metastasis is little known. The aim of this research was to investigate the role of TGFβ1-induced signalling pathways in oral cancer cell migration and to establish whether the inhibition of the associated pathway may be a suitable target for chemotherapeutic drug design to control oral cancer cell metastasis. Materials and Methods: SDS-PAGE and Western blot techniques were used to investigate the expression and phosphorylation status of TGFβ1induced key signalling molecules such as, SMAD, Akt and MAPK in normal keratinocytes and oral cancer cells. Gap closure and scatter assays were employed to study the effect of TGFβ1 on cell migration. Akt and MAPK inhibitors were also used to explore the role of associated signalling pathways in TGFβ1-induced cell migration. Phosphorylation of Akt, MAPK and SMAD were analysed by immunofluorescence in TGFβ1-induced migrated cells. Results: TGFβ1 stimulated the phosphorylation of SMAD, Akt and MAPK in both normal keratinocytes and oral cancer cells. The level of phosphorylation, however, depended upon cell type, time of exposure to and concentration of TGFβ1. TGFβ1-stimulated cancer cell migration both as single cells (EMT, epithelial to mesenchymal transition) and as a sheet of cells. Inhibitor assays confirmed that cancer cell migration is phosphorylated-Akt dependent. However, TGFβ1 did not stimulate migration as a sheet of cells, but EMT of normal keratinocytes which was phosphorylated-MAPK dependent. Conclusion: TGFβ1-induced oral cancer cell migration was dependent on the Akt signalling pathway. From this study, we propose that blocking the Akt pathway may inhibit oral cancer metastasis and could have potential in translating this research into clinical practice.

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Section: Discussioncontrasting

confidence: 64%

Is it all just an Akt - you’d be SMAD to believe it! Role of TGFβ1 in oral cancer metastasis

Alghamdi¹,

Shalgm²,

Ellis³

et al. 2018

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“…Recent studies have shown that the CSC-like phenotype is associated with activation of the PI3K/Akt/mTOR pathway in prostate cancer. 44,45 By inhibiting the C-terminal modulator protein, LETM1 promotes activation of Akt/PKB, 46 and overexpression of LETM1 may increase the activation of Akt in thyroid cancer cells. 23 In the present study, we found a significant positive correlation between the expression levels of LETM1 and pPI3K/pAkt.…”

Section: Discussionmentioning

confidence: 99%

<p>Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Is a Potential Prognostic Biomarker and Promotes Cell Progression in Prostate Cancer</p>

Piao¹,

Li²,

Feng³

et al. 2020

CMAR

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The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is a mitochondrial protein that has been associated with the occurrence and development of malignant tumors. Previous studies have shown that LETM1 expression is increased in several types of human cancer and is associated with a poor clinical outcome. However, the role of LETM1 in prostate cancer (PCa) has not yet been determined. In this study, we investigated the clinicopathological significance of LETM1 expression and its role in PCa progression. Methods: We assessed the expression of LETM1 and genes related to cancer stemness, epithelial-mesenchymal transition (EMT), cell cycle, and PI3K/Akt signaling in 133 paraffinembedded PCa tissue samples and cancer cells by using immunohistochemistry, immunofluorescence, and Western blotting. Results: LETM1 expression was significantly increased in PCa, and it was positively correlated with Gleason score, pathologic tumor (pT) stage, clinical stage, and high microvessel density. Survival analysis showed that patients with PCa with a high level of LETM1 expression exhibited a low overall survival. Cox regression analysis indicated that LETM1 is an independent poor prognostic PCa factor. Additionally, the expression of LETM1 was correlated with cancer cell stemness-associated genes, EMT-related genes, cell cycle regulatory genes, and PI3K/Akt signaling gene expression in PCa. Furthermore, knocking down LETM1 expression down-regulated the expression of stemness-related proteins, while inhibiting tumor spheroid formation, EMT-like changes, cell proliferation, migration, and invasion in PCa cells. Importantly, the PI3K inhibitor LY294002 strongly inhibited the expression of LETM1, pPI3K-p85, and pAkt (Thr308, Ser473) in PCa cells. Conclusion: These results indicate that LETM1 expression is associated with cancer cell stemness, promotes EMT-like changes and cell proliferation and is a potential prognostic biomarker for PCa.

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“…To interfere with receptor tyrosine kinase signaling, cells were also treated by Trk tyrosine receptor kinase inhibitor K252a (0.1 μM, Sigma, USA) for 24 hours. 26 Mimics control (NC mimics): 5′ UUG UAC UAC ACA AAA GUA CUG 3′), miR-10a-5p mimic: 5′ UAC CCU GUA GAU CCG AAU UUG UG 3′. BDNF for pcDNA3.0 (pc)-BDNF and pcDNA vector.…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…TrkB signaling is involved in the tumorigenicity of laryngeal cancer. 14 Thus, this study analyzed the relationship between TrkB and gender, age, smoking history, clinical stage, lymph node metastasis, and tumor site in patients with laryngeal cancer. At the same time, TrkB plays a role in laryngeal cancer cell proliferation, apoptosis, and cancer stem-like property, and the tumor growth in vivo.…”

Section: Introductionmentioning

confidence: 99%

<p>The Down-Regulation of TrkB Alleviates the Malignant Biological Behavior and Cancer Stem-Like Property of Laryngeal Cancer</p>

Zou

Liu

et al. 2020

CMAR

Self Cite

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Background: This study aimed to evaluate the effect of TrkB down-regulation on the malignant biological behavior and stem-like characteristics of laryngeal cancer. Methods: The relationship was analyzed between TrkB and clinicopathological parameters in patients with laryngeal cancer. The mRNA expressive levels of TrkB and miR-10a-5p were detected by qRT-PCR in laryngeal cancer tissues and cell lines. In vitro, Hep-2 and AMC-HN-8 cell proliferation, apoptosis and stem-like properties were detected by colony formation assay, flow cytometry, sphere formation, and Western blot, respectively. In vivo, the BALB/c nude mice model was used to evaluate the effect of TrkB on tumor growth. Results: The results showed that TrkB was related to smoking history, clinical stage, and lymph node metastasis, but had nothing to do with the gender, age, and tumor location of patients with laryngeal cancer. TrkB was highly expressed and miR-10a-5p was lowly expressed in laryngeal cancer tissues and cell lines. Down-regulation of TrkB inhibited Hep-2 and AMC-HN-8 cell proliferation and sphere formation as well as enhanced apoptosis, The result showed that miR-10a-5p bound to the 3ʹ-UTR of BDNF by a dual-luciferase reporter assay. Down-regulation of miR-10a-5p induced up-regulation of TrkB promoting development of laryngeal cancer. In vivo, down-regulation of TrkB suppressed tumor growth and inhibited the expression of stem-like marker proteins and promoted apoptosis. Conclusion: In conclusion, down-regulation of TrkB plays an important role in laryngeal cancer and is a promising target for future intervention strategies.

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TrkB promotes laryngeal cancer metastasis via activation PI3K/AKT pathway

Cited by 21 publications

References 37 publications

Is it all just an Akt - you’d be SMAD to believe it! Role of TGFβ1 in oral cancer metastasis

Is it all just an Akt - you’d be SMAD to believe it! Role of TGFβ1 in oral cancer metastasis

<p>Leucine Zipper-EF-Hand Containing Transmembrane Protein 1 Is a Potential Prognostic Biomarker and Promotes Cell Progression in Prostate Cancer</p>

<p>The Down-Regulation of TrkB Alleviates the Malignant Biological Behavior and Cancer Stem-Like Property of Laryngeal Cancer</p>

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