Targeting Cancer Stem Cell Markers or Pathways: A Potential Therapeutic Strategy for Oral Cancer Treatment

Lee, Jin Woo; Lee, Hwa-Yong

doi:10.15283/ijsc21084

Cited by 6 publications

(6 citation statements)

References 180 publications

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“…Inhibitors targeting stem-associated signaling pathways (Shh, Wnt/β-catenin, and Hippo) have been evaluated preclinically and clinically, and summarized elsewhere 408 . Surface molecules are not only critical biomarkers for CSC isolation but also potential targets for treatment 409 . Additionally, the interplay between CSCs, the TME, and metabolism has given us promising therapeutic targets.…”

Section: Prospects Of Targeting Cscsmentioning

confidence: 99%

Cancer stem cells: a target for overcoming therapeutic resistance and relapse

Zhang,

Yang,

Ouyang

et al. 2024

Cancer Biol Med

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Cancer stem cells (CSCs) are a small subset of cells in cancers that are thought to initiate tumorous transformation and promote metastasis, recurrence, and resistance to treatment. Growing evidence has revealed the existence of CSCs in various types of cancers and suggested that CSCs differentiate into diverse lineage cells that contribute to tumor progression. We may be able to overcome the limitations of cancer treatment with a comprehensive understanding of the biological features and mechanisms underlying therapeutic resistance in CSCs. This review provides an overview of the properties, biomarkers, and mechanisms of resistance shown by CSCs. Recent findings on metabolic features, especially fatty acid metabolism and ferroptosis in CSCs, are highlighted, along with promising targeting strategies. Targeting CSCs is a potential treatment plan to conquer cancer and prevent resistance and relapse in cancer treatment.

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Section: Prospects Of Targeting Cscsmentioning

confidence: 99%

Cancer stem cells: a target for overcoming therapeutic resistance and relapse

Zhang,

Yang,

Ouyang

et al. 2024

Cancer Biol Med

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“…At variance with normal basal stem cells, the stem-like cells present in OSCCs display low E-cadherin/β-catenin and high CD147/CD44 levels [ 41 ]. The concomitant overexpression of CD147 and CD44 makes the cancer stem cells present in OSCCs very viable and invasive [ 141 , 215 , 216 , 217 , 218 , 219 , 220 , 221 ]. In fact, while CD147 triggers MMP-9 expression, CD44 anchors MMP-9 in the invadopodia, thus enforcing and orienting cellular invasion [ 41 ].…”

Section: Cd147 and Oscc Resistance To Therapymentioning

confidence: 99%

“…Furthermore, CD44 stimulation upregulates the expression of multidrug transporters and multidrug resistance-associated proteins [ 41 ]. Accordingly, OSCCs rich in cancer stem cells are characterized by a high rate of relapse and metastasis and poor sensitivity to antitumor therapies [ 215 , 216 , 217 , 218 , 219 , 220 , 221 ].…”

Section: Cd147 and Oscc Resistance To Therapymentioning

confidence: 99%

“…In addition to being implicated in OSCC clinical progression, cancer stem cells are also likely to be involved in OSCC onset [ 221 ], as reported for other types of SCC, which originate from the malignant transformation of the stem cells of epithelium basal layers [ 225 ]. Nonetheless, carcinoma may also result from the dedifferentiation and subsequent transformation of mature epithelial cells [ 226 , 227 , 228 , 229 ].…”

Section: Cd147 and Oscc Resistance To Therapymentioning

confidence: 99%

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The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview

Barillari

Melaiu

Gargari

et al. 2022

IJMS

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Cluster of differentiation (CD)147, also termed extracellular matrix metalloprotease inducer or basigin, is a glycoprotein ubiquitously expressed throughout the human body, the oral cavity included. CD147 actively participates in physiological tissue development or growth and has important roles in reactive processes such as inflammation, immunity, and tissue repair. It is worth noting that deregulated expression and/or activity of CD147 is observed in chronic inflammatory or degenerative diseases, as well as in neoplasms. Among the latter, oral squamous cell carcinoma (OSCC) is characterized by an upregulation of CD147 in both the neoplastic and normal cells constituting the tumor mass. Most interestingly, the expression and/or activity of CD147 gradually increase as healthy oral mucosa becomes inflamed; hyperplastic/dysplastic lesions are then set on, and, eventually, OSCC develops. Based on these findings, here we summarize published studies which evaluate whether CD147 could be employed as a marker to monitor OSCC development and progression. Moreover, we describe CD147-promoted cellular and molecular events which are relevant to oral carcinogenesis, with the aim to provide useful information for assessing whether CD147 may be the target of novel therapeutic approaches directed against OSCC.

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“…Through binding interactions of CD44 with its natural ligands, such as hyaluronic acid or other binding partners secreted in the extracellular matrix, a series of signaling cascades in OSCC cells may be activated, leading to the enhanced tumor growth, metastatic ability, and resistance to cancer treatment [ 16 ]. Therefore, targeting CD44 and its signaling pathways that involve in the cancer-promoting activities has emerged as a novel therapeutic potential for OSCC [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

CD44 Mediates Oral Squamous Cell Carcinoma-Promoting Activity of MRE11 via AKT Signaling

Yuan

Hung

Hsu

et al. 2022

JPM

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Oral cancer is one of the highest-incidence malignancies worldwide, with the occurrence of oral squamous cell carcinoma (OSCC) being the most frequently diagnosed form. A barrier for oral cancer management may arise from tumor cells that possess properties of cancer stemness, which has been recognized as a crucial factor in tumor recurrence and metastasis. As such, understanding the molecular mechanisms underlying these tumor cells may provide insights for improving cancer treatment. MRE11 is the core protein of the RAD50/MRE11/NBS1 complex with a primary role in DNA damage repair, and it has been diversely associated with tumor development including OSCC. In this study, we aimed to investigate the engagement of CD44, a cancer stemness marker functioning in the control of cell growth and motility, in OSCC malignancy under the influence of MRE11. We found that overexpression of MRE11 enhanced CD44 expression and tumorsphere formation in OSCC cells, whereas knockdown of MRE11 reduced these phenomena. In addition, the MRE11-promoted tumorsphere formation or cell migration ability was compromised in OSCC cells carrying siRNA that targets CD44, as was the MRE11-promoted AKT phosphorylation. These were further supported by analyzing clinical samples, where higher CD44 expression was associated with lymph node metastasis. Additionally, a positive correlation between the expression of MRE11 and CD44, or that of CD44 and phosphorylated AKT, was observed in OSCC tumor tissues. Finally, the expression of CD44 was found to be higher in the metastatic lung nodules from mice receiving tail vein-injection with MRE11-overexpressing OSCC cells compared with control mice, and a positive correlation between CD44 and phosphorylated AKT was also observed in these metastatic lung nodules. Altogether, our current study revealed a previously unidentified mechanism linking CD44 and AKT in MRE11-promoted OSCC malignancy, which may shed light to the development of novel therapeutic strategies in consideration of this new pathway in OSCC.

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Targeting Cancer Stem Cell Markers or Pathways: A Potential Therapeutic Strategy for Oral Cancer Treatment

Cited by 6 publications

References 180 publications

Cancer stem cells: a target for overcoming therapeutic resistance and relapse

Cancer stem cells: a target for overcoming therapeutic resistance and relapse

The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview

CD44 Mediates Oral Squamous Cell Carcinoma-Promoting Activity of MRE11 via AKT Signaling

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