Isoform-specific functions of Numb in breast cancer progression, metastasis and proteome remodeling

Zhang, Y; Se, Dho; Cd, Simpson; Othman, Kamal; Bondoc, Andrew; Cj, McGlade

doi:10.1101/2021.02.01.429237

Cited by 2 publications

(2 citation statements)

References 51 publications

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“…The mechanisms via which Numb's exon 9 contribute to cancer are unknown. Evidence suggests that the exon 9 may counteract the tumor-suppressive actions of Exon9sk Numb proteins, in addition to a potential gain-of-function acquired from increased Exon9in expression [ 98 ].…”

Section: Stem Cells Of the Mammary Glandmentioning

confidence: 99%

Asymmetric cell division of mammary stem cells

Chhabra

Booth

2021

Cell Div

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Somatic stem cells are distinguished by their capacity to regenerate themselves and also to produce daughter cells that will differentiate. Self-renewal is achieved through the process of asymmetric cell division which helps to sustain tissue morphogenesis as well as maintain homeostasis. Asymmetric cell division results in the development of two daughter cells with different fates after a single mitosis. Only one daughter cell maintains “stemness” while the other differentiates and achieves a non-stem cell fate. Stem cells also have the capacity to undergo symmetric division of cells that results in the development of two daughter cells which are identical. Symmetric division results in the expansion of the stem cell population. Imbalances and deregulations in these processes can result in diseases such as cancer. Adult mammary stem cells (MaSCs) are a group of cells that play a critical role in the expansion of the mammary gland during puberty and any subsequent pregnancies. Furthermore, given the relatively long lifespans and their capability to undergo self-renewal, adult stem cells have been suggested as ideal candidates for transformation events that lead to the development of cancer. With the possibility that MaSCs can act as the source cells for distinct breast cancer types; understanding their regulation is an important field of research. In this review, we discuss asymmetric cell division in breast/mammary stem cells and implications on further research. We focus on the background history of asymmetric cell division, asymmetric cell division monitoring techniques, identified molecular mechanisms of asymmetric stem cell division, and the role asymmetric cell division may play in breast cancer.

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Section: Stem Cells Of the Mammary Glandmentioning

confidence: 99%

Asymmetric cell division of mammary stem cells

Chhabra

Booth

2021

Cell Div

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“…NUMB endocytic adaptor protein (NUMB) is an endocytic adaptor protein that has various functions in cell polarity maintenance, cell migration, and EMT. The importance of NUMB AS has been reported in various cancers including breast[ 61 , 62 ], lung cancer[ 63 ], and hepatocellular carcinoma cells[ 64 ]. Four NUMB isoforms based on the AS of exon 3 and exon 9 have been identified in vertebrates[ 65 ].…”

Section: Main Textmentioning

confidence: 99%

Alternative RNA splicing in stem cells and cancer stem cells: Importance of transcript-based expression analysis

Ebrahimie

Rahimirad

Tahsili

et al. 2021

WJSC

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Alternative ribonucleic acid (RNA) splicing can lead to the assembly of different protein isoforms with distinctive functions. The outcome of alternative splicing (AS) can result in a complete loss of function or the acquisition of new functions. There is a gap in knowledge of abnormal RNA splice variants promoting cancer stem cells (CSCs), and their prospective contribution in cancer progression. AS directly regulates the self-renewal features of stem cells (SCs) and stem-like cancer cells. Notably, octamer-binding transcription factor 4A spliced variant of octamer-binding transcription factor 4 contributes to maintaining stemness properties in both SCs and CSCs. The epithelial to mesenchymal transition pathway regulates the AS events in CSCs to maintain stemness. The alternative spliced variants of CSCs markers, including cluster of differentiation 44, aldehyde dehydrogenase, and doublecortin-like kinase , α6β1 integrin, have pivotal roles in increasing self-renewal properties and maintaining the pluripotency of CSCs. Various splicing analysis tools are considered in this study. LeafCutter software can be considered as the best tool for differential splicing analysis and identification of the type of splicing events. Additionally, LeafCutter can be used for efficient mapping splicing quantitative trait loci. Altogether, the accumulating evidence re-enforces the fact that gene and protein expression need to be investigated in parallel with alternative splice variants.

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Isoform-specific functions of Numb in breast cancer progression, metastasis and proteome remodeling

Cited by 2 publications

References 51 publications

Asymmetric cell division of mammary stem cells

Asymmetric cell division of mammary stem cells

Alternative RNA splicing in stem cells and cancer stem cells: Importance of transcript-based expression analysis

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