Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin

Badarinath, Krithika; Dam, Binita; Kataria, Sunny; Zirmire, Ravindra K.; Dey, Rakesh; Kansagara, Gaurav; Ajnabi, Johan; Hegde, Akshay; Singh, Randhir; Masudi, Tafheem; Sambath, Janani; Sachithanandan, Sasikala P.; Kumar, Prashant; Gulyani, Akash; He, You–Wen; Krishna, Sudhir

doi:10.1016/j.celrep.2022.111390

Cited by 8 publications

(6 citation statements)

References 86 publications

(116 reference statements)

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“…Snail is a transcription factor known to be a driver of the EMT, a process involved in the maintenance of cancer stem cells and metastasis [ 209 ]. When Snail is overexpressed in the mouse epidermis, epidermal stem/progenitor cell populations expand, and stemness is promoted [ 165 , 166 , 210 ]. In turn, Snail induces the transcription of Mindin (SPON2) matricellular protein, which binds to integrin αMβ2 (CD11b) in an autocrine manner and activates c-Src and STAT3.…”

Section: Matricellular Proteins In Stem Cell Regulation During Homeos...mentioning

confidence: 99%

“…In turn, Snail induces the transcription of Mindin (SPON2) matricellular protein, which binds to integrin αMβ2 (CD11b) in an autocrine manner and activates c-Src and STAT3. Loss of function in Mindin was further shown to rescue the effect of Snail overexpression on epidermal expansion and in squamous cell carcinoma xenograft models [ 165 ]. In addition, a higher SNAI1 expression was found in the epidermis of patients with systemic sclerosis, linking its function in skin fibrosis to the induction of inflammation and fibroblast-mediated collagen secretion [ 167 , 168 ].…”

Section: Matricellular Proteins In Stem Cell Regulation During Homeos...mentioning

confidence: 99%

“…In aged hair follicle stem cells, Mindin / Spon2 gene expression is decreased while Thbs1 is increased [ 112 ]. The role of Mindin in hair follicle stem cells has not been reported, although it may be related to stemness, as in the case of epidermal stem cells [ 165 ]. Hair follicle stem cell activation is associated with the skin vasculature [ 212 , 213 ].…”

Section: Matricellular Proteins In Stem Cell Regulation During Homeos...mentioning

confidence: 99%

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Matricellular Proteins in the Homeostasis, Regeneration, and Aging of Skin

Raja,

Clarin,

Yanagisawa

2023

IJMS

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Matricellular proteins are secreted extracellular proteins that bear no primary structural functions but play crucial roles in tissue remodeling during development, homeostasis, and aging. Despite their low expression after birth, matricellular proteins within skin compartments support the structural function of many extracellular matrix proteins, such as collagens. In this review, we summarize the function of matricellular proteins in skin stem cell niches that influence stem cells’ fate and self-renewal ability. In the epidermal stem cell niche, fibulin 7 promotes epidermal stem cells’ heterogeneity and fitness into old age, and the transforming growth factor-β—induced protein ig-h3 (TGFBI)—enhances epidermal stem cell growth and wound healing. In the hair follicle stem cell niche, matricellular proteins such as periostin, tenascin C, SPARC, fibulin 1, CCN2, and R-Spondin 2 and 3 modulate stem cell activity during the hair cycle and may stabilize arrector pili muscle attachment to the hair follicle during piloerections (goosebumps). In skin wound healing, matricellular proteins are upregulated, and their functions have been examined in various gain-and-loss-of-function studies. However, much remains unknown concerning whether these proteins modulate skin stem cell behavior, plasticity, or cell–cell communications during wound healing and aging, leaving a new avenue for future studies.

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Section: Matricellular Proteins In Stem Cell Regulation During Homeos...mentioning

confidence: 99%

Section: Matricellular Proteins In Stem Cell Regulation During Homeos...mentioning

confidence: 99%

Section: Matricellular Proteins In Stem Cell Regulation During Homeos...mentioning

confidence: 99%

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Matricellular Proteins in the Homeostasis, Regeneration, and Aging of Skin

Raja,

Clarin,

Yanagisawa

2023

IJMS

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“…Some of these proteins, including OCT4, MYC, KLF4, and SOX2 (Yamanaka factors), are universal, considering that they are typical of both cancer and normal stem cells and are considered essential for stem-related phenotypes [ 107 ]. The regulation of other markers, though, for instance, NANOG, BMI-1, SNAIL, ALDHs, LGR5, CXCR4, REX-1, Musashi-1, LETM1, and C-met, is considered to be dependent on both the cancer type and the specific phenotype of the CSCs that we want to analyze (e.g., drug-resistant, tumorigenic, metastatic) [ 35 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 ]. Studying the expression of specific genes both at the transcriptional and translation level, as well as the activity and localization of these proteins, is useful in assessing the enrichment of CSC properties [ 118 , 119 , 120 , 121 , 122 , 123 ].…”

Section: Cancer Stem Cells (Cscs)mentioning

confidence: 99%

The Concept of Cancer Stem Cells: Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression

Tsochantaridis

Roupas

Mohlin

et al. 2023

Life

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Cancer is a multifactorial, complex disease exhibiting extraordinary phenotypic plasticity and diversity. One of the greatest challenges in cancer treatment is intratumoral heterogeneity, which obstructs the efficient eradication of the tumor. Tumor heterogeneity is often associated with the presence of cancer stem cells (CSCs), a cancer cell sub-population possessing a panel of stem-like properties, such as a self-renewal ability and multipotency potential. CSCs are associated with enhanced chemoresistance due to the enhanced efflux of chemotherapeutic agents and the existence of powerful antioxidant and DNA damage repair mechanisms. The distinctive characteristics of CSCs make them ideal targets for clinical therapeutic approaches, and the identification of efficient and specific CSCs biomarkers is of utmost importance. Aldehyde dehydrogenases (ALDHs) comprise a wide superfamily of metabolic enzymes that, over the last years, have gained increasing attention due to their association with stem-related features in a wide panel of hematopoietic malignancies and solid cancers. Aldehyde dehydrogenase 1B1 (ALDH1B1) is an isoform that has been characterized as a marker of colon cancer progression, while various studies suggest its importance in additional malignancies. Here, we review the basic concepts related to CSCs and discuss the potential role of ALDH1B1 in cancer development and its contribution to the CSC phenotype.

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“…42,43 Finally, more recent findings have shown that Twist1 plays an important role in maintaining stemness in a number of different tissue specific stem cell compartments. [44][45][46][47][48][49][50][51] Bmi1, 52,53 Snail, 54 and Slug 55 have been shown to regulate epithelial cell identity by promoting stem-like/progenitor states. Furthermore, Twist1 has been shown to elevate the expression of cancer testis antigens (CTAs) such as NY-ESO1 and MAGEA4 in ESCC.…”

Section: Twist1mentioning

confidence: 99%

Twist1 as a target for prevention of cutaneous squamous cell carcinoma

Wang

Rho

Eguiarte-Solomon³

et al. 2022

Molecular Carcinogenesis

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Cutaneous squamous cell carcinoma (cSCC) represents an important clinical problem requiring novel approaches for both prevention and treatment. The transcription factor, Twist-related protein 1 (Twist1), has been identified as having a key mechanistic role in the development and progression of cSCC. Studies in relevant mouse models of cSCC have shown that Twist1 regulates epithelial-mesenchymal transition (EMT) and stemness driving progression and metastasis of cSCC. In addition, further research has shown that Twist1 regulates the balance between keratinocyte proliferation and differentiation and therefore impacts earlier stages of cSCC development. Through use of keratinocyte specific Twist1 knockout models, a role for this gene in keratinocyte stem cell homeostasis has been revealed. As a transcription factor, Twist1 regulates a large number of genes both in a positive, as well as a negative manner across several interdependent pathways. Studies in keratinocyte specific knockout models have shown that Twist1 upregulates the expression of genes involved in proliferation, stemness, and EMT while downregulating the expression of genes associated with differentiation. Furthermore, a number of compounds, including naturally occurring compounds, have been identified that target Twist1 and can block its effects in cancer cells and in keratinocytes in vivo. Collectively, the current understanding of Twist1 function in cSCC development and progression suggests that it represents a potential target for prevention and treatment of cSCC.

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Snail maintains the stem/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin

Cited by 8 publications

References 86 publications

Matricellular Proteins in the Homeostasis, Regeneration, and Aging of Skin

Matricellular Proteins in the Homeostasis, Regeneration, and Aging of Skin

The Concept of Cancer Stem Cells: Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression

Twist1 as a target for prevention of cutaneous squamous cell carcinoma

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