Tcf3 promotes cell migration and wound repair through regulation of lipocalin 2

Miao, Qi; Ku, Amy T.; Nishino, Yudai; Howard, Jeffrey; Rao, Ajay S; Shaver, Timothy M.; Garcia, Gloria E.; Le, Diep; Karlin, Kristen L.; Westbrook, Thomas F.; Poli, Valeria; Nguyen, Hoang

doi:10.1038/ncomms5088

Cited by 65 publications

(76 citation statements)

References 71 publications

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“…TCF3 can function as a transcriptional repressor and activator and has been implicated in skin homoeostasis and wound healing47. Our data suggest an important role in cuSCC development as well (Supplementary Fig.…”

Section: Resultssupporting

confidence: 53%

Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

et al. 2016

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Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible.

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Section: Resultssupporting

confidence: 53%

Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

et al. 2016

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“…Recently it has been shown to be important in wound repair and can mediate some of its effects through NGAL. Tcf3 induces NGAL which promotes cell migration and wound healing [43].…”

Section: Novel Functions Of Ngal/lipocalinsmentioning

confidence: 99%

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

Candido

Abrams

Steelman

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Various, diverse molecules contribute to the tumor microenvironment and influence invasion and metastasis. In this review, the roles of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) in the tumor microenvironment and sensitivity to therapy will be discussed. The lipocalin family of proteins has many important functions. For example when NGAL forms a complex with MMP-9 it increases its stability which is important in cancer metastasis. Small hydrophobic molecules are bound by NGAL which can alter their entry into and efflux from cells. Iron transport and storage are also influenced by NGAL activity. Regulation of iron levels is important for survival in the tumor microenvironment as well as metastasis. Innate immunity is also regulated by NGAL as it can have bacteriostatic properties. NGAL and MMP-9 expression may also affect the sensitivity of cancer cells to chemotherapy as well as targeted therapy. Thus NGAL and MMP-9 play important roles in key processes involved in metastasis as well as response to therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

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“…The transcription factor, Stat3, is an upstream regulator of Tcf3. 63 Lipocalinderived peptides may be promising tools to develop new formulations to aid wound healing (Fig. 3D).…”

Section: Peptide Modulation Of Mmp Expressionmentioning

confidence: 99%

Metalloproteinases and Wound Healing

Caley¹,

Martins²,

O’Toole³

2015

Advances in Wound Care

674

503

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Significance: Matrix metalloproteinases (MMPs) are present in both acute and chronic wounds. They play a pivotal role, with their inhibitors, in regulating extracellular matrix degradation and deposition that is essential for wound reepithelialization. The excess protease activity can lead to a chronic nonhealing wound. The timed expression and activation of MMPs in response to wounding are vital for successful wound healing. MMPs are grouped into eight families and display extensive homology within these families. This homology leads in part to the initial failure of MMP inhibitors in clinical trials and the development of alternative methods for modulating the MMP activity. MMP-knockout mouse models display altered wound healing responses, but these are often subtle phenotypic changes indicating the overlapping MMP substrate specificity and inter-MMP compensation. Recent Advances: Recent research has identified several new MMP modulators, including photodynamic therapy, protease-absorbing dressing, microRNA regulation, signaling molecules, and peptides. Critical Issues: Wound healing requires the controlled activity of MMPs at all stages of the wound healing process. The loss of MMP regulation is a characteristic of chronic wounds and contributes to the failure to heal. Future Directions: Further research into how MMPs are regulated should allow the development of novel treatments for wound healing. SCOPE AND SIGNIFICANCEThis review highlights recent advances in understanding the regulation of matrix metalloproteinases (MMPs) in skin and how this knowledge might be applied in patients to improve wound healing. Selected recent advances include microRNA (MiR) regulation, novel peptides, signal transduction, experimental therapies, and novel dressings. TRANSLATIONAL RELEVANCEWound healing is a complex multicellular process involving fibroblasts, keratinocytes, and endothelial cells as well as inflammatory cells. The healing process follows an orderly sequence of events incorporating four distinct, yet overlapping, phases: hemostasis, the inflammatory phase, the proliferation phase, and the remodeling phase. The phases of wound healing are regulated by cross talk between different groups of molecules, including extracellular matrix (ECM), integrins, growth factors, and MMPs. Migration of cells on ECM, and remodeling and degradation of the ECM by MMPs are key elements of wound repair. CLINICAL RELEVANCEChronic wounds, including pressure sores, venous ulcers, and diabetic ulcers, are a major clinical problem with considerable morbidity and associated financial costs. Excessive MMPs are a feature of chronic wounds. Regulation of MMP levels in wounds could lead to improved wound healing. OVERVIEWThe MMP family is a group of calcium-dependent zinc-containing enzymes that are involved in the degradation of ECM. Family members share structural ( Fig. 1) and sequence similarities, a flexible proline-rich hinge region, and a hemopexinlike C-terminal domain, which functions in recognition of substrates (usually ECM). Excep...

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Tcf3 promotes cell migration and wound repair through regulation of lipocalin 2

Cited by 65 publications

References 71 publications

Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

Metalloproteinases and Wound Healing

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