Binding of Galectin-3, a β-Galactoside-binding Lectin, to MUC1 Protein Enhances Phosphorylation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) and Akt, Promoting Tumor Cell Malignancy

Mori, Yoshihide; Akita, Kaoru; Yashiro, Masakazu; Sawada, Tetsuji; Hirakawa, Kosei; Murata, Takeomi; Nakada, Hiroshi

doi:10.1074/jbc.m115.651489

Cited by 51 publications

(39 citation statements)

References 57 publications

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“…Revealing the function of galectins and glycoconjugates during blastocyst implantation and the pathogenesis of ectopic pregnancy requires identfication of the glycoconjugates, especially those carrying α2,6‐sialyltion. Mucin 1 (MUC1) is recognized by galectins (Jeschke et al, ; Mori et al, ), making it a candidate glycoprotein that may associate with galectins in the Fallopian tube and uterus. MUC1 is a highly glycosylated protein whose decreased surface expression allows blastocysts to implant at the endometrium in normal pregnancy as well as on the Fallopian tube epithelium in tubal ectopic pregnancy (Aplin et al, ; Savaris et al, ; Al‐Azemi et al, ).…”

Section: Discussionmentioning

confidence: 99%

Cigarette smoking alters sialylation in the Fallopian tube of women, with implications for the pathogenesis of ectopic pregnancy

Nio‐Kobayashi

Abidin

Brown

et al. 2016

Molecular Reproduction Devel

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Section: Discussionmentioning

confidence: 99%

Cigarette smoking alters sialylation in the Fallopian tube of women, with implications for the pathogenesis of ectopic pregnancy

Nio‐Kobayashi

Abidin

Brown

et al. 2016

Molecular Reproduction Devel

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“…In this way, MUC1-C has the capacity to promote loss of polarity with induction of the epithelial-mesenchymal transition (EMT) [3, 4] and thereby interact with other cell surface molecules, including receptor tyrosine kinases (RTKs) [5–12]. The available evidence has further supported the premise that (i) MUC1-C functions in activating multiple pathways linked to EMT, self-renewal and survival, and (ii) the overexpression of MUC1-C, as found in diverse human carcinomas, represents a subversion and appropriation of these functions by cancer cells to promote their own growth and immortality [1, 13].…”

Section: Introductionmentioning

confidence: 99%

MUC1-C Oncoprotein Integrates a Program of EMT, Epigenetic Reprogramming and Immune Evasion in Human Carcinomas

Rajabi

Küfe

2017

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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The MUC1 gene evolved in mammalian species to provide protection of epithelia. The transmembrane MUC1 C-terminal subunit (MUC1-C) signals stress to the interior of the epithelial cell and, when overexpressed as in most carcinomas, functions as an oncoprotein. MUC1-C induces the epithelial-mesenchymal transition (EMT) by activating the inflammatory NF-κB p65 pathway and, in turn, the EMT-transcriptional repressor ZEB1. Emerging evidence has indicated that MUC1-C drives a program integrating the induction of EMT with activation of stem cell traits, epigenetic reprogramming and immune evasion. This mini-review focuses on the potential importance of this MUC1-C program in cancer progression.

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“…They are involved in metastatic processes and in cancer drug resistance . Indeed, it has been shown that Gal‐3 is overexpressed with its ligand MUC1 in malignant tumor cells and induces MUC1 clustering on the tumor cell surface by binding to the TF tumor‐associated antigen . Taking advantage of the Gal‐3 CRD–MUC1 interaction, tumor cells, like intravascular malignant cells, invade vessels and survive in the circulation avoiding anoikis .…”

Section: Introductionmentioning

confidence: 99%

Molecular Recognition of a Thomsen–Friedenreich Antigen Mimetic Targeting Human Galectin‐3

et al. 2018

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Overexpression of the Thomsen-Friedenreich (TF) antigen in cell membrane proteins occurs in 90 % of adenocarcinomas. Additionally, the binding of the TF antigen to human galectin-3 (Gal-3), also frequently overexpressed in malignancy, promotes cancer progression and metastasis. In this context, structures that interfere with this specific interaction have the potential to prevent cancer metastasis. A multidisciplinary approach combining the optimized synthesis of a TF antigen mimetic with NMR, X-ray crystallography methods, and isothermal titration calorimetry assays was used to unravel the molecular structural details that govern the Gal-3/TF mimetic interaction. The TF mimetic has a binding affinity for Gal-3 similar to that of the TF natural antigen and retains the binding epitope and bioactive conformation observed for the native antigen. Furthermore, from a thermodynamic perspective, a decrease in the enthalpic contribution was observed for the Gal-3/TF mimetic complex; however, this behavior is compensated by a favorable gain in entropy. From a structural perspective, these results establish our TF mimetic as a scaffold to design multivalent solutions to potentially interfere with Gal-3 aberrant interactions and for likely use in hampering Gal-3-mediated cancer cell adhesion and metastasis.

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Binding of Galectin-3, a β-Galactoside-binding Lectin, to MUC1 Protein Enhances Phosphorylation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) and Akt, Promoting Tumor Cell Malignancy

Cited by 51 publications

References 57 publications

Cigarette smoking alters sialylation in the Fallopian tube of women, with implications for the pathogenesis of ectopic pregnancy

Cigarette smoking alters sialylation in the Fallopian tube of women, with implications for the pathogenesis of ectopic pregnancy

MUC1-C Oncoprotein Integrates a Program of EMT, Epigenetic Reprogramming and Immune Evasion in Human Carcinomas

Molecular Recognition of a Thomsen–Friedenreich Antigen Mimetic Targeting Human Galectin‐3

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