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(searched for: doi:10.4103/jcrt.jcrt_482_17)
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Pei Xu, Lei Wang, Bin Mo, Xiao Xie, Rui Hu, Lianyong Jiang, Fengqing Hu, ,
Published: 1 February 2023
Frontiers in Oncology, Volume 12; https://doi.org/10.3389/fonc.2022.985827

Abstract:
Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, which is a severer threaten to human health because of its extremely high morbidity and mortality. In this study, the role of Notchless homolog 1 (NLE1) in the development of NSCLC was investigated and the underlying mechanism was explored. The outcomes showed that NLE1 expression is significantly higher in tumor tissues than normal tissues, and is correlated with the pathological stage. The regulation of NSCLC development by NLE1 was also visualized by the in vitro and in vivo loss-of-function studies, which indicated the inhibition of cell growth and migration, as well as enhancement of cell apoptosis on condition of NLE1 knockdown. As for the mechanism, it was demonstrated that NLE1 may execute its tumor-regulating function through activating E2F1-mediated transcription of CDK1, and PI3K/Akt signaling pathway was also supposed as a downstream of NLE1 in the regulation of NSCLC. Both CDK1 overexpression and treatment of Akt pathway activator could reverse the NLE1 knockdown induced NSCLC inhibition to some extent. In conclusion, this study identified NLE1 as a novel tumor promotor in the development and progression of NSCLC, which may be a potential therapeutic target in the treatment of NSCLC.
, Dhrishya Dharmapal,
Published: 26 May 2022
Frontiers in Immunology, Volume 13; https://doi.org/10.3389/fimmu.2022.876278

Abstract:
Although the role of microtubule dynamics in cancer progression is well-established, the roles of tubulin isotypes, their cargos and their specific function in the induction and sustenance of cancer stem cells (CSCs) were poorly explored. But emerging reports urge to focus on the transport function of tubulin isotypes in defining orchestrated expression of functionally critical molecules in establishing a stem cell niche, which is the key for CSC regulation. In this review, we summarize the role of specific tubulin isotypes in the transport of functional molecules that regulate metabolic reprogramming, which leads to the induction of CSCs and immune evasion. Recently, the surface expression of GLUT1 and GRP78 as well as voltage-dependent anion channel (VDAC) permeability, regulated by specific isotypes of β-tubulins have been shown to impart CSC properties to cancer cells, by implementing a metabolic reprogramming. Moreover, βIVb tubulin is shown to be critical in modulating EphrinB1signaling to sustain CSCs in oral carcinoma. These tubulin-interacting molecules, Ephrins, GLUT1 and GRP78, are also important regulators of immune evasion, by evoking PD-L1 mediated T-cell suppression. Thus, the recent advances in the field implicate that tubulins play a role in the controlled transport of molecules involved in CSC niche. The indication of tubulin isotypes in the regulation of CSCs offers a strategy to specifically target those tubulin isotypes to eliminate CSCs, rather than the general inhibition of microtubules, which usually leads to therapy resistance.
Giuseppina Chiappara, Serena Di Vincenzo, Claudia Sangiorgi, Caterina Di Sano, Claudia D'Anna, Giovanni Zito, , Patrizio Vitulo, Alessandro Bertani,
Published: 5 November 2021
Toxicology Letters, Volume 355, pp 31-40; https://doi.org/10.1016/j.toxlet.2021.11.002

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Dandan Wei, Xinghao Zhu, Shanshan Li, Guangyao Liu, Yongkun Wang, Wei Wang, Qiao Zhang,
Biochemical and Biophysical Research Communications, Volume 554, pp 206-213; https://doi.org/10.1016/j.bbrc.2020.12.055

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