Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells

Reis, Jhenifer Santos dos; Santos, Marcos André Rodrigues da Costa; Costa, Kelli Monteiro da; Freire-de-Lima, Célio Geraldo; Morrot, Alexandre; Previato, José O.; Mendonça-Previato, Lúcia; Fonseca, Leonardo Marques da; Freire-de-Lima, Leonardo

doi:10.1016/j.matbio.2023.03.002

Cited by 8 publications

(11 citation statements)

References 83 publications

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“…Indeed, in addition to regulating the EMT program, p53 can also modulate the extracellular matrix (ECM). Accumulating evidence has demonstrated that ECM remodeling promotes the development and maintenance of stemness and chemoresistance [ 78 , 79 , 80 , 81 ]. ECM is composed of collagen, non-collagenous glycoproteins (mainly fibronectin and laminin), and proteoglycans.…”

Section: Role Of P53 In Dox Resistancementioning

confidence: 99%

“…Moreover, the interleukin-6 (IL-6) produced by CAFs can reduce the response of p53 to DOX [ 105 ]. In addition to increasing the levels of MRPs and anti-apoptotic proteins, chronic exposure to DOX induces an MDR phenotype in drug-resistant MCF-7 cells through the upregulation of the ECM glycoprotein pp-GalNAc-T6 (which mainly constitutes carcinoembryonic fibronectin) [ 80 ]. The integrin-dependent downregulation of p53 levels in melanoma, sarcoma, and fibroblasts results in increased cell survival and resistance to apoptosis [ 106 ].…”

Section: Role Of P53 In Dox Resistancementioning

confidence: 99%

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p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act

Guo

Tang²,

et al. 2023

Nutrients

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Doxorubicin (DOX) is a highly effective chemotherapeutic drug, but its long-term use can cause cardiotoxicity and drug resistance. Accumulating evidence demonstrates that p53 is directly involved in DOX toxicity and resistance. One of the primary causes for DOX resistance is the mutation or inactivation of p53. Moreover, because the non-specific activation of p53 caused by DOX can kill non-cancerous cells, p53 is a popular target for reducing toxicity. However, the reduction in DOX-induced cardiotoxicity (DIC) via p53 suppression is often at odds with the antitumor advantages of p53 reactivation. Therefore, in order to increase the effectiveness of DOX, there is an urgent need to explore p53-targeted anticancer strategies owing to the complex regulatory network and polymorphisms of the p53 gene. In this review, we summarize the role and potential mechanisms of p53 in DIC and resistance. Furthermore, we focus on the advances and challenges in applying dietary nutrients, natural products, and other pharmacological strategies to overcome DOX-induced chemoresistance and cardiotoxicity. Lastly, we present potential therapeutic strategies to address key issues in order to provide new ideas for increasing the clinical use of DOX and improving its anticancer benefits.

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Section: Role Of P53 In Dox Resistancementioning

confidence: 99%

Section: Role Of P53 In Dox Resistancementioning

confidence: 99%

p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act

Guo

Tang²,

et al. 2023

Nutrients

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“…In addition, there is a direct relationship between chemical resistance and the expression of abnormal glycans in cancer cells [125]. Inhibition of N-glycosylation can affect the expression of EGFR and IGF1R, and enhance the sensitivity of PAAD cells to chemotherapy drugs [126].…”

Section: Cancer Chemoresistancementioning

confidence: 99%

Mucin Glycans: A Target for Cancer Therapy

Sun,

Zhang,

et al. 2023

Molecules

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Mucin glycans are an important component of the mucus barrier and a vital defence against physical and chemical damage as well as pathogens. There are 20 mucins in the human body, which can be classified into secreted mucins and transmembrane mucins according to their distributions. The major difference between them is that secreted mucins do not have transmembrane structural domains, and the expression of each mucin is organ and cell-specific. Under physiological conditions, mucin glycans are involved in the composition of the mucus barrier and thus protect the body from infection and injury. However, abnormal expression of mucin glycans can lead to the occurrence of diseases, especially cancer, through various mechanisms. Therefore, targeting mucin glycans for the diagnosis and treatment of cancer has always been a promising research direction. Here, we first summarize the main types of glycosylation (O-GalNAc glycosylation and N-glycosylation) on mucins and the mechanisms by which abnormal mucin glycans occur. Next, how abnormal mucin glycans contribute to cancer development is described. Finally, we summarize MUC1-based antibodies, vaccines, radio-pharmaceuticals, and CAR-T therapies using the best characterized MUC1 as an example. In this section, we specifically elaborate on the recent new cancer therapy CAR-M, which may bring new hope to cancer patients.

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“…Following that thread, we recently published a paper showing that inducing a MDR phenotype in breast cancer cells, leads to the overexpression of GALNT6. However, not only that, reducing the expression of GALNT6 also promoted a partial reversion of the resistance phenotype, showing that this glysosyltransferase, as well as onf-FN, may play a direct role not only in the activation of EMT and promotion of metastasis, but also in the acquisition of resistance phenotypes [ 61 ] ( Figure 2 ). Other enzymes of the same family have been ascribed important roles in cancer progression.…”

Section: Unusual O -Linked Glycan Structures and T...mentioning

confidence: 99%

Bittersweet Sugars: How Unusual Glycan Structures May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer

et al. 2023

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Increased expression of the pathological O-glycosylated form of oncofetal fibronectin in the multidrug resistance phenotype of cancer cells

Cited by 8 publications

References 83 publications

p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act

p53 at the Crossroads between Doxorubicin-Induced Cardiotoxicity and Resistance: A Nutritional Balancing Act

Mucin Glycans: A Target for Cancer Therapy

Bittersweet Sugars: How Unusual Glycan Structures May Connect Epithelial-to-Mesenchymal Transition and Multidrug Resistance in Cancer

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