Inhibition of CD44 sensitizes cisplatin-resistance and affects Wnt/β-catenin signaling in HNSCC cells

S, Roy; Kar, Madhabananda; Roy, Shomereeta; Padhi, Swatishree; Kumar, Amit; Thakur, Shilpa; Akhter, Yusuf; Gatto, Gianluca; Banerjee, Birendranath

doi:10.1016/j.ijbiomac.2020.01.131

Cited by 38 publications

(34 citation statements)

References 51 publications

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“…208 Furthermore, Wnt signaling is a key pathway regulating the well-known SC marker CD44 by directly interacting with the promoter and presenting castration resistance. 209 Combined with the research conducted by Souvick Roy, 210 these findings indicate a positive feedback mechanism between CD44 and Wnt: CD44 binds to β-catenin and activates Wnt, resulting in cispatin resistance. In addition, the transcription factor Sox8 was reported to promote the Wnt/β-catenin pathway by binding to the promoter of FZD7, eventually leading to cisplatin resistance.…”

Section: Resistance Mechanisms Of Cscsmentioning

confidence: 81%

Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents

Zhang

et al. 2021

Sig Transduct Target Ther

248

167

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Cancer stem cells (CSCs) show a self-renewal capacity and differentiation potential that contribute to tumor progression and therapy resistance. However, the underlying processes are still unclear. Elucidation of the key hallmarks and resistance mechanisms of CSCs may help improve patient outcomes and reduce relapse by altering therapeutic regimens. Here, we reviewed the identification of CSCs, the intrinsic and extrinsic mechanisms of therapy resistance in CSCs, the signaling pathways of CSCs that mediate treatment failure, and potential CSC-targeting agents in various tumors from the clinical perspective. Targeting the mechanisms and pathways described here might contribute to further drug discovery and therapy.

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Section: Resistance Mechanisms Of Cscsmentioning

confidence: 81%

Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents

Zhang

et al. 2021

Sig Transduct Target Ther

248

167

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“…The clinical relevance of CD44 expression level was -amongst others -assessed by Nasman and colleagues, who also observed improved survival in patients with low CD44 expression and HPV + status (34). Furthermore, CD44 was shown to be associated with the important WNT/β-catenin signaling cascade, with a key role in carcinogenesis and therapeutic resistance (35). Roy and colleagues demonstrated that CD44 inhibition sensitized cisplatin-resistant HNSCC cells (35).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, CD44 was shown to be associated with the important WNT/β-catenin signaling cascade, with a key role in carcinogenesis and therapeutic resistance (35). Roy and colleagues demonstrated that CD44 inhibition sensitized cisplatin-resistant HNSCC cells (35). Additionally, others have investigated the important link between CD44 expression and EGFR signaling, where high CD44 expression was found to be associated with p16 − tumors and with higher EGFR expression (36).…”

Section: Discussionmentioning

confidence: 99%

Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV⁺ and HPV⁻ Squamous Cell Carcinoma

Kansy¹,

Aderhold

Huber

et al. 2020

Cancer Genomics Proteomics

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Background: We investigated the expression patterns of cluster of differentiation (CD) 44 and amphiregulin (AREG), two signaling molecules essential for cell proliferation and differentiation, under the influence of selective tyrosine kinase inhibitors (TKIs) in human papillomavirus (HPV) + and HPV − squamous carcinoma cell lines. Materials and Methods: The protein expression of CD44 and AREG was determined by sandwich enzymelinked immunosorbent assay in HPV − cell lines UMSCC-11A and UMSCC-14C, and HPV + CERV-196 cells after TKI treatment. Results: The expression of AREG and CD44 was dependent on the cell line's HPV status. AREG expression increased after incubation with nilotinib in HPV + tumor cells. The expression of CD44 was significantly influenced by all drugs; its expression under selective epidermal growth factor receptor inhibition was mostly reduced, whereas nilotinib led to an exceptional increase of CD44 expression. Conclusion: The selective drug treatment options significantly influenced the expression of CD44 and AREG in HPV − and HPV + tumor cells, constituting the need for personalized treatment options.

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“…Elaboration of CDDP resistance mechanisms using tumor cell lines has revealed that survival of tumor cells in cisplatin-treated conditions primarily relies on adaptive mechanisms that enable tumor cells in switching to oncogenic mode which enable evasion of cytotoxicity in drug treated conditions [ 13 ]. Thus, utilizing cell lines as models mechanisms mediated through intra-tumoral oncogenes, mutations and signaling cascades, as well as extra-tumoral factors, such as stromal components and non-cellular components, have been identified to affect CDDP sensitivity [ 10 , 14 , 15 , 16 , 17 ]. Multiple mechanisms mediated by oncogenes, such as exosomal-microRNAs and cell signaling pathways, were identified to promote CDDP-insensitivity in neuroblastoma [ 10 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Amino Acids Regulate Cisplatin Insensitivity in Neuroblastoma

Gunda

Pathania

Chava

et al. 2020

Cancers

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Neuroblastoma are pediatric, extracranial malignancies showing alarming survival prognosis outcomes due to their resilience to current aggressive treatment regimens, including chemotherapies with cisplatin (CDDP) provided in the first line of therapy regimens. Metabolic deregulation supports tumor cell survival in drug-treated conditions. However, metabolic pathways underlying cisplatin-resistance are least studied in neuroblastoma. Our metabolomics analysis revealed that cisplatin-insensitive cells alter their metabolism; especially, the metabolism of amino acids was upregulated in cisplatin-insensitive cells compared to the cisplatin-sensitive neuroblastoma cell line. A significant increase in amino acid levels in cisplatin-insensitive cells led us to hypothesize that the mechanisms upregulating intracellular amino acid pools facilitate insensitivity in neuroblastoma. We hereby report that amino acid depletion reduces cell survival and cisplatin-insensitivity in neuroblastoma cells. Since cells regulate their amino acids levels through processes, such as autophagy, we evaluated the effects of hydroxychloroquine (HCQ), a terminal autophagy inhibitor, on the survival and amino acid metabolism of cisplatin-insensitive neuroblastoma cells. Our results demonstrate that combining HCQ with CDDP abrogated the amino acid metabolism in cisplatin-insensitive cells and sensitized neuroblastoma cells to sub-lethal doses of cisplatin. Our results suggest that targeting of amino acid replenishing mechanisms could be considered as a potential approach in developing combination therapies for treating neuroblastomas.

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Inhibition of CD44 sensitizes cisplatin-resistance and affects Wnt/β-catenin signaling in HNSCC cells

Cited by 38 publications

References 51 publications

Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents

Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents

Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV⁺ and HPV⁻ Squamous Cell Carcinoma

Amino Acids Regulate Cisplatin Insensitivity in Neuroblastoma

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Inhibition of CD44 sensitizes cisplatin-resistance and affects Wnt/β-catenin signaling in HNSCC cells

Cited by 38 publications

References 51 publications

Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents

Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents

Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV+ and HPV− Squamous Cell Carcinoma

Amino Acids Regulate Cisplatin Insensitivity in Neuroblastoma

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Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV⁺ and HPV⁻ Squamous Cell Carcinoma