The SOX2 Status of Disseminated Tumor Cells in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy

Krawczyk, Natalia; Janowski, Kathrin; Banys‐Paluchowski, Maggie; Staebler, Annette; Neubauer, Hans; Meisner, Christoph; Hartkopf, Andreas; Brucker, Sara Y.; Wallwiener, D.; Fehm, Tanja

doi:10.21873/anticanres.15066

Cited by 2 publications

(2 citation statements)

References 56 publications

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“…In breast cancer (BC), SOX2 contributes to tumour malignancy and causes cells to display stromal-like features [ 41 ]. Recent studies have reported that SOX2 induces resistance to radiotherapy in BC, which plays a pivotal role in the emergence of chemotherapy resistance in tumor cells [ 17 , 42 ]. In this study, it is noteworthy that SOX2 expression was affected in cells treated with PSMD7 knockdown and overexpression.…”

Section: Discussionmentioning

confidence: 99%

Deubiquitinase PSMD7 facilitates pancreatic cancer progression through activating Nocth1 pathway via modifying SOX2 degradation

Luo,

Yu,

Zhu

et al. 2024

Cell Biosci

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Background Ubiquitination is a critical post-translational modification which can be reversed with an enzyme family known as deubiquitinating enzymes (DUBs). It has been reported that dysregulation of deubiquitination leads to carcinogenesis. As a member of the DUBs family, proteasome 26 S subunit non-ATPase 7 (PSMD7) serves as an underlying tumour-promoting factor in multiple cancers. However, the clinical significance and biological functions of PSMD7 in pancreatic cancer (PC) remain unclear. Results In this study, we first reported frequent overexpression of PSMD7 in PC tissues, and high levels of PSMD7 were markedly linked to shorter survival and a malignant phenotype in PC patients. An array of in vitro and in vivo gain/loss-of-function tests revealed that PSMD7 facilitates the progression of PC cells. Additionally, we found that PSMD7 promotes PC cell progression by activating the Notch homolog 1 (Notch1) signalling. Interestingly, in PC cells, the inhibitory effect of PSMD7 knockdown on cellular processes was comparable to that observed upon Notch1 knockdown. Mechanistically, PSMD7 deubiquitinated and stabilised sex determining region Y (SRY)-box 2 (SOX2), a key mediator of Notch1 signalling. The stabilisation of SOX2, mediated by PSMD7, dramatically increased SOX2 protein levels, subsequently activating the Notch1 pathway. Finally, restoration of SOX2 expression abrogated the PSMD7-silenced antitumour effect. Conclusions Taken together, our work identifies and validates PSMD7 as a promoter of PC progression through augmentation of the Notch1 signalling pathway mediated by SOX2. This finding suggests that PSMD7 holds promise as a potential therapeutic target for the management of this refractory disease.

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Section: Discussionmentioning

confidence: 99%

Deubiquitinase PSMD7 facilitates pancreatic cancer progression through activating Nocth1 pathway via modifying SOX2 degradation

Luo,

Yu,

Zhu

et al. 2024

Cell Biosci

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“…Previous studies found a discordance between the HER2 status of the PT and DTCs in 29–49% of cases [ 20 , 25 , 26 , 27 ]. These results are in line with the 44% discordance found in the present study when solely differentiating between “HER2-positive” and “HER2-negative”.…”

Section: Discussionmentioning

confidence: 99%

Comparing the HER2 Status of the Primary Tumor to That of Disseminated Tumor Cells in Early Breast Cancer

Volmer,

Dannehl,

Matovina

et al. 2024

IJMS

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Breast cancer remains a leading cause of cancer mortality in women globally. Despite advancements in systemic therapy, the risk of distant recurrence persists even after such treatment and may be linked to disseminated tumor cells (DTCs). Variability in molecular characteristics between primary tumors (PTs) and distant metastases underscores the need to comprehensively understand metastatic pathways. This retrospective study investigated discrepancies between HER2 expression in PTs and DTCs and their implications for survival outcomes in 201 early breast cancer (EBC) patients. We found a significant association between HER2 expression in PTs and DTCs when classifying tumors as HER2-high/low/negative. Patients whose HER2 status was discordant between PTs and DTCs exhibited worse distant disease-free survival than those with concordant status. Multivariate analysis confirmed the HER2 status of DTCs as an independent prognostic factor for distant DFS. These findings emphasize the importance of assessing HER2 expression in DTCs and its potential implications for tailored therapy strategies in EBC. Furthermore, prospective trials are needed to validate these findings and explore targeted therapies based on the molecular characteristics of DTCs.

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The SOX2 Status of Disseminated Tumor Cells in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy

Cited by 2 publications

References 56 publications

Deubiquitinase PSMD7 facilitates pancreatic cancer progression through activating Nocth1 pathway via modifying SOX2 degradation

Deubiquitinase PSMD7 facilitates pancreatic cancer progression through activating Nocth1 pathway via modifying SOX2 degradation

Comparing the HER2 Status of the Primary Tumor to That of Disseminated Tumor Cells in Early Breast Cancer

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