Amyloid precursor protein promotes the migration and invasion of breast cancer cells by regulating the MAPK signaling pathway

Xiong, Weining; Chen, Shuanglong; Lu, Chuanhui

doi:10.3892/ijmm.2019.4404

Cited by 36 publications

(32 citation statements)

References 47 publications

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“…Incidentally, genes that are strongly associated to neurodegenerative disorders, i.e., because their products are the main constituents of hallmark brain deposits and they may lead to early-onset inherited disease forms, do not exhibit typical features of oncogenes or tumor suppressors but appears to be involved in some processes associated to cancers. For example, APP promotes migration and invasion of breast cancer cells [ 47 ] and is a predictor of poor prognosis in some breast cancers [ 48 ]; whereas alpha-synuclein may be implicated in the malignant progression of meningioma [ 49 ]. A recent analysis of cancer incidence in carriers of FTDP-17 MAPT mutations showed increased risk of developing cancer [ 50 ].…”

Section: Coming Together: Cancer and Neurodegenerative Disorders mentioning

confidence: 99%

Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer

Papin

Paganetti

2020

Brain Sciences

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Neurodegenerative disorders and cancer may appear unrelated illnesses. Yet, epidemiologic studies indicate an inverse correlation between their respective incidences for specific cancers. Possibly explaining these findings, increasing evidence indicates that common molecular pathways are involved, often in opposite manner, in the pathogenesis of both disease families. Genetic mutations in the MAPT gene encoding for TAU protein cause an inherited form of frontotemporal dementia, a neurodegenerative disorder, but also increase the risk of developing cancer. Assigning TAU at the interface between cancer and neurodegenerative disorders, two major aging-linked disease families, offers a possible clue for the epidemiological observation inversely correlating these human illnesses. In addition, the expression level of TAU is recognized as a prognostic marker for cancer, as well as a modifier of cancer resistance to chemotherapy. Because of its microtubule-binding properties, TAU may interfere with the mechanism of action of taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network and impair cell division. Indeed, a low TAU expression is associated to a better response to taxanes. Although TAU main binding partners are microtubules, TAU is able to relocate to subcellular sites devoid of microtubules and is also able to bind to cancer-linked proteins, suggesting a role of TAU in modulating microtubule-independent cellular pathways associated to oncogenesis. This concept is strengthened by experimental evidence linking TAU to P53 signaling, DNA stability and protection, processes that protect against cancer. This review aims at collecting literature data supporting the association between TAU and cancer. We will first summarize the evidence linking neurodegenerative disorders and cancer, then published data supporting a role of TAU as a modifier of the efficacy of chemotherapies and of the oncogenic process. We will finish by addressing from a mechanistic point of view the role of TAU in de-regulating critical cancer pathways, including the interaction of TAU with cancer-associated proteins.

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Section: Coming Together: Cancer and Neurodegenerative Disorders mentioning

confidence: 99%

Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer

Papin

Paganetti

2020

Brain Sciences

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“…As expected, collagen proteins tightly connected GISTs and adipose endothelial cells spatially (Figure 5B). CD74 were found to be highly involved in such interactions by binding secreted proteins and cell surface receptors, such as MIF, APP, and COPA (Figure 5B), thus are likely to playing an important role in promoting tumor progression, according to previous research 45‐48 …”

Section: Resultsmentioning

confidence: 62%

Single‐cell transcriptome analysis revealed the heterogeneity and microenvironment of gastrointestinal stromal tumors

et al. 2021

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Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the human gastrointestinal tract. In this study, we performed single‐cell RNA sequencing (RNA‐seq) on intra‐ and peri‐tumor tissues from GIST patients with the aim of discovering the heterogeneity of tumor cells in GIST and their interactions with other cells. We found four predominating cell types in GIST tumor tissue, including T cells, macrophages, tumor cells, and NK cells. Tumor cells could be clustered into two groups: one was highly proliferating and associated with high risk of metastasis, the other seemed “resting” and associated with low risk. Their clinical relevance and prognostic values were confirmed by RNA‐seq of 65 GIST samples. T cells were the largest cell type in our single‐cell data. Two groups of CD8+ effector memory (EM) cells were in the highest clonal expansion and performed the highest cytotoxicity but were also the most exhausted among all T cells. A group of macrophages were found polarized to possess both M1 and M2 signatures, and increased along with tumor progression. Cell‐to‐cell interaction analysis revealed that adipose endothelial cells had high interactions with tumor cells to facilitate their progression. Macrophages were at the center of the tumor microenvironment, recruiting immune cells to the tumor site and having most interactions with both tumor and nontumor cells. In conclusion, we obtained an overview of the GIST microenvironment and revealed the heterogeneity of each cell type and their relevance to risk classifications, which provided a novel theoretical basis for learning and curing GISTs.

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“…The human β-amyloid precursor protein (APP), due to its function as a cell surface receptor, participates in numerous biological processes, such as cell growth, adhesion, and axonogenesis [ 29 ]. Recently, several pathophysiological functions of APP have been proposed in different human diseases such as neurodevelopmental [ 30 ], autism [ 31 ], amyotrophic lateral sclerosis [ 32 ], multiple sclerosis [ 33 ], Alzheimer’s disease [ 34 ], and cancer [ 35 – 37 ].…”

Section: Discussionmentioning

confidence: 99%

Abnormal expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma based on data mining

et al. 2020

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Background EPB41L1 gene (erythrocyte membrane protein band 4.1 like 1) encodes the protein 4.1N, a member of 4.1 family, playing a vital role in cell adhesion and migration, which is associated with the malignant progression of various human cancers. However, the expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma (KIRC) remain to be investigated. Methods In this study, we collected the mRNA expression of EPB41L1 in KIRC through the Oncomine platform, and used the HPA database to perform the pathological tissue immunohistochemistry in patients. Then, the sub-groups and prognosis of KIRC were performed by UALCAN and GEPIA web-tool, respectively. Further, the mutation of EPB41L1 in KIRC was analyzed by c-Bioportal. The co-expression genes of EPB41L1 in KIRC were displayed from the LinkedOmics database, and function enrichment analysis was used by LinkFinder module in LinkedOmics. The function of EPB41L1 in cell adhesion and migration was confirmed by wound healing assay using 786-O cells in vitro. Co-expression gene network was constructed through the STRING database, and the MCODE plug-in of which was used to build the gene modules, both of them was visualized by Cytoscape software. Finally, the top modular genes in the same patient cohort were constructed through data mining in TCGA by using the UCSC Xena browser. Results The results indicated that EPB41L1 was down-expressed in KIRC, leading to a poor prognosis. Moreover, there is a mutation in the FERM domain of EPB41L1, but it has no significant effect on the prognosis of KIRC. The co-expressed genes of EPB41L1 were associated with cell adhesion and confirmed in vitro. Further analysis suggested that EPB41L1 and amyloid beta precursor protein (APP) were coordinated to regulated cancer cell adhesion, thereby increasing the incidence of cancer cell metastasis and tumor invasion. Conclusions In summary, EPB41L1 is constantly down-expressed in KIRC tissues, resulting a poor prognosis. Therefore, we suggest that it can be an effective biomarker for the diagnosis of KIRC.

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Amyloid precursor protein promotes the migration and invasion of breast cancer cells by regulating the MAPK signaling pathway

Cited by 36 publications

References 47 publications

Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer

Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer

Single‐cell transcriptome analysis revealed the heterogeneity and microenvironment of gastrointestinal stromal tumors

Abnormal expression and prognostic significance of EPB41L1 in kidney renal clear cell carcinoma based on data mining

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