AJUBA: A regulator of epidermal homeostasis and cancer

Schleicher, Krista; Schramek, Daniel

doi:10.1111/exd.14272

Cited by 13 publications

(17 citation statements)

References 113 publications

(302 reference statements)

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“…CDKN2A is a well-known tumour suppressor gene in several cancer types, including SCC 27 . AJUBA is a regulator of epidermal homeostasis and has been implicated in SCC as well 27,28 . Less is known about BCORL1 (BCL6 corepressor like 1).…”

Section: Discussionmentioning

confidence: 99%

A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in histologically healthy tissues

Luijts

Elliott

Siaw

et al. 2022

Preprint

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Recent research on histologically healthy human tissues identified omnipresent mutational microclones, driven by somatic mutations known to be responsible for carcinogenesis (e.g., in TP53 or NOTCH1). These new insights are fundamentally changing current tumour evolution models, with broad oncological implications. Most studies are based on surgical remnant tissues, which are not available for many organs and rarely in a pan-organ setting (multiple organs from the same individual). Here, we describe an approach based on clinically annotated post-mortem tissues, derived from whole-body donors that are routinely used for educational purposes at human anatomy units. We validated this post-mortem approach using UV-exposed and unexposed epidermal skin tissues and confirm the presence of positively selected NOTCH1/2-, TP53- and FAT1-driven clones. No selection signals were detected in a set of immune genes or housekeeping genes. Additionally, we provide the first evidence for smoking-induced clonal changes in oral epithelia, likely underlying the origin of head and neck carcinogenesis. In conclusion, the whole-body donor-based approach provides a nearly unlimited healthy tissue resource to study mutational clonality and gain fundamental mutagenic insights in the presumed earliest stages of tumour evolution.

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Section: Discussionmentioning

confidence: 99%

A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in histologically healthy tissues

Luijts

Elliott

Siaw

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…CDKN2A is a well-known tumor suppressor gene in several cancer types, including SCC 27 . AJUBA is a regulator of epidermal homeostasis and has been implicated in SCC as well 27 , 28 . Less is known about BCORL1 (BCL6 corepressor like 1).…”

Section: Discussionmentioning

confidence: 99%

A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues

Luijts

Elliott

Siaw

et al. 2022

Sci Rep

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Recent research on normal human tissues identified omnipresent clones of cells, driven by somatic mutations known to be responsible for carcinogenesis (e.g., in TP53 or NOTCH1). These new insights are fundamentally changing current tumor evolution models, with broad oncological implications. Most studies are based on surgical remnant tissues, which are not available for many organs and rarely in a pan-organ setting (multiple organs from the same individual). Here, we describe an approach based on clinically annotated post-mortem tissues, derived from whole-body donors that are routinely used for educational purposes at human anatomy units. We validated this post-mortem approach using UV-exposed and unexposed epidermal skin tissues and confirm the presence of positively selected NOTCH1/2-, TP53- and FAT1-driven clones. No selection signals were detected in a set of immune genes or housekeeping genes. Additionally, we provide the first evidence for smoking-induced clonal changes in oral epithelia, likely underlying the origin of head and neck carcinogenesis. In conclusion, the whole-body donor-based approach provides a nearly unlimited healthy tissue resource to study mutational clonality and gain fundamental mutagenic insights in the presumed earliest stages of tumor evolution.

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“…49,63 Decades of studies have elucidated diverse molecular mechanisms regulating EpSC self-renewal and differentiation, as detailed in a comprehensive review by Guan et al 64 in this special issue. EpSCs also represent one of the key cellular sources for skin cancers such as squamous cell carcinoma and basal cell carcinoma, [65][66][67] been made in this field, as documented in the review article by Guan et al 64 Moreover, in this issue, Schleicher et al 68 provide an interesting review for one of the key players-AJUBA, a scaffolding protein that plays a critical role during epidermal homeostasis and skin cancer formation. AJUBA has diverse roles in modulating and tuning different pathways, likely acting as a molecular switchboard to control multiple signalling pathways at the same time to regulate EpSC behaviours.…”

Section: Epidermal S Tem Cell Smentioning

confidence: 99%