Cytoskeleton protein 4.1R suppresses murine keratinocyte cell hyperproliferation via activating the Akt/ERK pathway in an EGFR-dependent manner

Chen, Lixiang; Wang, Ting; Ji, Xiang; Ding, Cong; Liang, Taotao; Liu, Xin; Lu, Jike; Guo, Xinrui; Kang, Qiaozhen; Ji, Zhenyu

doi:10.1016/j.yexcr.2019.111648

Cited by 8 publications

(7 citation statements)

References 40 publications

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“…Most evidence has shown that the activation of canonical (P65) and non‐canonical (P52/100) NF‐ κ B is critical for signal transduction of B‐cell CSR stimulated by LPS. 4.1R acts as an adaptor between the cell membrane and cytoskeleton proteins that are involved in many intercellular signal transductions, such as extracellular‐regulated kinase and phosphoinositide 3‐kinase signaling 25,42 . However, to our knowledge, whether 4.1R regulates the NF‐ κ B signaling pathway is still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…4.1R acts as an adaptor between the cell membrane and cytoskeleton proteins that are involved in many intercellular signal transductions, such as extracellular-regulated kinase and phosphoinositide 3-kinase signaling. 25,42 However, to our knowledge, whether 4.1R regulates the NF-jB signaling pathway is still unknown. Here, our results demonstrated that 4.1R impacts LPS-mediated B-cell fate by activating and regulating the canonical rather than the non-canonical NF-jB signaling pathway.…”

Section: Co-localization Of 41r and Tlr4 In B Cellsmentioning

confidence: 99%

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Cytoskeleton protein 4.1R regulates B‐cell fate by modulating the canonical NF‐κB pathway

Liang

Guo

et al. 2020

Immunology

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During the immune response, B cells can enter the memory pathway, which is characterized by class switch recombination (CSR), or they may undergo plasma cell differentiation (PCD) to secrete immunoglobulin. Both of these processes occur in activated B cells, which are reported to relate to membrane-association proteins and adaptors. Protein 4.1R acts as an adaptor, linking membrane proteins to the cytoskeleton, and is involved in many cell events such as cell activation and differentiation, and cytokine secretion. However, the effect of 4.1R on regulating B-cell fate is unclear. Here, we show an important association between B-cell fate and 4.1R. In vitro, primary B cells were stimulated with lipopolysaccharide combined with interleukin-4; results showed that 4.1R-deficient (4.1R-/-) cells compared with wild-type (4.1R +/+) B cells augmented expression of activation-induced cytidine deaminase and germline, resulting in increased IgG1 + B cells, whereas the secretion of IgG1 and IgM was reduced, and CD138 + B cells were also decreased. Throughout the process, 4.1R regulated canonical nuclear factor (NF-jB) rather than non-canonical NF-jB to promote the expression of CSR complex components, leading to up-regulation of B-cell CSR. In contrast, 4.1R-deficient B cells showed reduced expression of Blimp-1, which caused B cells to down-regulate PCD. Furthermore, over-activation of canonical NF-jB may induce apoptosis signaling to cause PCD apoptosis to reduce PCD number. In summary, our results suggest that 4.1R acts as a B-cell fate regulator by inhibiting the canonical NF-jB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Co-localization Of 41r and Tlr4 In B Cellsmentioning

confidence: 99%

Cytoskeleton protein 4.1R regulates B‐cell fate by modulating the canonical NF‐κB pathway

Liang

Guo

et al. 2020

Immunology

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“…Erythrocyte membrane protein band 4.1 (EPB41) links cell membrane proteins to the cytoskeleton and is involved in many cellular processes such as cell proliferation, cytokine secretion, cell adhesion, and cell migration [29][30][31][32][33][34]. EPB41 suppresses epidermal growth factor receptor (EGFR) activation [29] and thus plays an important role as a tumor suppressor in cancer development. Dysregulation and excessive activation of EGFR leads to the hyperproliferation of many cell types such as epidermal keratinocytes and thus has been linked to tumorigenesis in SCC [78,79].…”

Section: Discussionmentioning

confidence: 99%

“…Rare variants significantly associated with KC across several association test methods are shown in Table 3 and Figure 2. Several of the genes described here can be assigned to categories that are involved in the development of solid tumors: MC1R is involved in pigmentation/UV protection [27,28], EPB41 [29][30][31][32][33][34] and MYCT [35][36][37][38] in tumor suppression, and ADGRG3 in immunomodulation [39][40][41][42]. Studies on MGME1 suggest a direct involvement in cancer development and progression [43,44], and finally upregulation of the EPH8A gene expression was associated with a poor prognosis in ovarian, oral tongue, and gastric cancers [45][46][47].…”

Section: Rare Variantsmentioning

confidence: 99%

Identification of Genetic Risk Factors for Keratinocyte Cancer in Immunosuppressed Solid Organ Transplant Recipients: A Case-Control Study

Sunder‐Plaßmann

Geusau

Endler

et al. 2023

Cancers

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Because of long-term immunosuppression, solid organ transplant recipients are at increased risk for keratinocyte cancer. We matched solid organ transplant patients (n = 150), cases with keratinocyte cancers and tumor-free controls, considering the most important risk factors for keratinocyte cancer in solid organ transplant recipients. Using whole exome data of germline DNA from this patient cohort, we identified several genetic loci associated with the occurrence of multiple keratinocyte cancers. We found one genome-wide significant association of a common single nucleotide polymorphism located in EXOC3 (rs72698504). In addition, we found several variants with a p-value of less than 10−5 associated with the number of keratinocyte cancers. These variants were located in the genes CYB561, WASHC1, PITRM1-AS1, MUC8, ABI3BP, and THBS2-AS1. Using whole exome sequencing data, we performed groupwise tests for rare missense variants in our dataset and found robust associations (p < 10−6, Burden Zeggini test) between MC1R, EPHA8, EPO, MYCT1, ADGRG3, and MGME1 and keratinocyte cancer. Thus, overall, we detected genes involved in pigmentation/UV protection, tumor suppression, immunomodulation, intracellular traffic, and response to UV as genetic risk factors for multiple keratinocyte cancers in solid organ transplant recipients. We also grouped selected genes to pathways and found a selection of genes involved in the “cellular response to UV” to be significantly associated with multiple keratinocyte cancers.

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“…Cytoskeleton protein 4.1 can often regulate the progression of cancer by inhibiting the growth and survival of tumor cells during the malignant transformation of cells [ 7 ]. Tumor cells can utilize intracellularly related signaling pathways to promote their malignant features, while cytoskeleton protein 4.1 often inhibits cancer progression via interaction with multiple signaling pathways [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Cytoskeleton Protein 4.1 in Immunotherapy

Yuan

Chen

et al. 2023

IJMS

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Cytoskeleton protein 4.1 is an essential class of skeletal membrane protein, initially found in red blood cells, and can be classified into four types: 4.1R (red blood cell type), 4.1N (neuronal type), 4.1G (general type), and 4.1B (brain type). As research progressed, it was discovered that cytoskeleton protein 4.1 plays a vital role in cancer as a tumor suppressor. Many studies have also demonstrated that cytoskeleton protein 4.1 acts as a diagnostic and prognostic biomarker for tumors. Moreover, with the rise of immunotherapy, the tumor microenvironment as a treatment target in cancer has attracted great interest. Increasing evidence has shown the immunoregulatory potential of cytoskeleton protein 4.1 in the tumor microenvironment and treatment. In this review, we discuss the role of cytoskeleton protein 4.1 within the tumor microenvironment in immunoregulation and cancer development, with the intention of providing a new approach and new ideas for future cancer diagnosis and treatment.

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Cytoskeleton protein 4.1R suppresses murine keratinocyte cell hyperproliferation via activating the Akt/ERK pathway in an EGFR-dependent manner

Cited by 8 publications

References 40 publications

Cytoskeleton protein 4.1R regulates B‐cell fate by modulating the canonical NF‐κB pathway

Cytoskeleton protein 4.1R regulates B‐cell fate by modulating the canonical NF‐κB pathway

Identification of Genetic Risk Factors for Keratinocyte Cancer in Immunosuppressed Solid Organ Transplant Recipients: A Case-Control Study

The Role of Cytoskeleton Protein 4.1 in Immunotherapy

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