NOTCH pathway inactivation reprograms stem-like oral cancer cells to JAK-STAT dependent state and provides the opportunity of synthetic lethality

Ghosh, Subhashis; Mitra, Paromita; Saha, Uday; Nandi, Rimpa; Jena, Subhashree; Ghosh, Arnab; Roy, Shantanu Saha; Acharya, Moulinath; Biswas, Nidhan K.; Singh, Sandeep

doi:10.1016/j.tranon.2023.101669

Cited by 5 publications

(1 citation statement)

References 72 publications

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“…These findings were in support of the antitumor activity of JAK-inhibitors such as Ruxolitinib and Tofacitinib, both of which reduced the hostile tumor proliferation and stemness, in addition to the downregulated Notch-signaling. The addition of γ-secretase inhibitors like LY411575 or RO4929097 helps oral CSCs maintain the Notch-inactive state and following them with the above JAK inhibitors could be a potential therapy option ( 202 ). Silencing novel pathways like the FAS-ERK-JAG1-NOTCH1 axis could also result in decreasing the OSCC stemness and the risk of pulmonary metastases, making this a good target for advanced therapies in the future ( 203 ).…”

Section: Stratagems In Targeting Pathways Involved In Oscc Stemness –...mentioning

confidence: 99%

Panoramic view of key cross-talks underpinning the oral squamous cell carcinoma stemness - unearthing the future opportunities

Vastrad,

Ritesh,

et al. 2023

Front. Oncol.

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The clinical management of oral cancer is often frequented with challenges that arise from relapse, recurrence, invasion and resistance towards the cornerstone chemo and radiation therapies. The recent conceptual advancement in oncology has substantiated the role of cancer stem cells (CSC) as a predominant player of these intricacies. CSC are a sub-group of tumor population with inherent adroitness to self-renew with high plasticity. During tumor evolution, the structural and functional reprogramming persuades the cancer cells to acquire stem-cell like properties, thus presenting them with higher survival abilities and treatment resistance. An appraisal on key features that govern the stemness is of prime importance to confront the current challenges encountered in oral cancer. The nurturing niche of CSC for maintaining its stemness characteristics is thought to be modulated by complex multi-layered components encompassing neoplastic cells, extracellular matrix, acellular components, circulatory vessels, various cascading signaling molecules and stromal cells. This review focuses on recapitulating both intrinsic and extrinsic mechanisms that impart the stemness. There are contemplating evidences that demonstrate the role of transcription factors (TF) in sustaining the neoplastic stem cell’s pluripotency and plasticity alongside the miRNA in regulation of crucial genes involved in the transformation of normal oral mucosa to malignancy. This review illustrates the interplay between miRNA and various known TF of oral cancer such as c-Myc, SOX, STAT, NANOG and OCT in orchestrating the stemness and resistance features. Further, the cross-talks involved in tumor micro-environment inclusive of cytokines, macrophages, extra cellular matrix, angiogenesis leading pathways and influential factors of hypoxia on tumorigenesis and CSC survival have been elucidated. Finally, external factorial influence of oral microbiome gained due to the dysbiosis is also emphasized. There are growing confirmations of the possible roles of microbiomes in the progression of oral cancer. Given this, an attempt has been made to explore the potential links including EMT and signaling pathways towards resistance and stemness. This review provides a spectrum of understanding on stemness and progression of oral cancers at various regulatory levels along with their current therapeutic knowledge. These mechanisms could be exploited for future research to expand potential treatment strategies.

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Section: Stratagems In Targeting Pathways Involved In Oscc Stemness –...mentioning

confidence: 99%

Panoramic view of key cross-talks underpinning the oral squamous cell carcinoma stemness - unearthing the future opportunities

Vastrad,

Ritesh,

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

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Targeting signaling pathways in cancer stem cells: A potential approach for developing novel anti-cancer therapeutics

Sinha,

Hembram,

Chatterjee

2024

International Review of Cell and Molecular Biology

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Secretase promotes AD progression: simultaneously cleave Notch and APP

Yang,

Zhang,

Feng

et al. 2024

Front. Aging Neurosci.

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Alzheimer’s disease (AD) involves complex pathological mechanisms. Secretases include membrane protein extracellular structural domain proteases and intramembrane proteases that cleave the topology to type I or type II. Secretases can effectively regulate the activation of Notch and amyloid precursor protein (APP), key factors in the progression of AD and cancer. This article systematically summarizes the intracellular localization, cleavage sites and products, and biological functions of six subtypes of secretases (α-secretase, β-secretase, γ-secretase, δ-secretase, ε-secretase, and η-secretase), and for the first time, elucidates the commonalities and differences between these subtypes of secretases. We found that each subtype of secretase primarily cleaves APP and Notch as substrates, regulating Aβ levels through APP cleavage to impact the progression of AD, while also cleaving Notch receptors to affect cancer progression. Finally, we review the chemical structures, indications, and research stages of various secretase inhibitors, emphasizing the promising development of secretase inhibitors in the fields of cancer and AD.

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NOTCH pathway inactivation reprograms stem-like oral cancer cells to JAK-STAT dependent state and provides the opportunity of synthetic lethality

Cited by 5 publications

References 72 publications

Panoramic view of key cross-talks underpinning the oral squamous cell carcinoma stemness - unearthing the future opportunities

Panoramic view of key cross-talks underpinning the oral squamous cell carcinoma stemness - unearthing the future opportunities

Targeting signaling pathways in cancer stem cells: A potential approach for developing novel anti-cancer therapeutics

Secretase promotes AD progression: simultaneously cleave Notch and APP

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