Small breast epithelial mucin (SBEM) has the potential to be a marker for predicting hematogenous micrometastasis and response to neoadjuvant chemotherapy in breast cancer

Liu, Zhaozhe; Xie, Xiaodong; Qu, Shuxian; Zheng, Zhendong; Wang, Yakun

doi:10.1007/s10585-010-9323-2

Cited by 18 publications

(14 citation statements)

References 30 publications

(29 reference statements)

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“…Several studies have now shown that MUCL1 expression strongly correlates with higher tumor grade, 4 TNM (tumor, node, metastases) staging and lymph node metastasis. 3, 5 Most recently, it was shown that high MUCL1 expression is significantly correlated with high recurrence and death rates in triple negative breast cancer patients. 6 …”

Section: Introductionmentioning

confidence: 99%

HER2 drives Mucin-like 1 to control proliferation in breast cancer cells

Conley¹,

Bosco²,

Tice³

et al. 2016

Oncogene

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Mucin-like 1 (MUCL1) was first identified as a breast-specific gene over a decade ago. Based on its highly restricted mRNA expression in breast tissue and continued expression during breast tumorigenesis and progression, MUCL1 is an attractive tumor-associated antigen and a potential therapeutic target. However, very little is known about the cellular location, biological functions and regulation of the MUCL1 protein, which will have a major impact on its druggability. Here we describe our efforts to fully characterize the cellular localization of MUCL1, investigate its regulation by key breast cancer oncogenes such as human epidermal growth factor receptor 2 (HER2) and discover its functional roles in breast cancer. Although some mucins are membrane bound, our data indicate that MUCL1 is secreted by some breast cancer cells, whereas others only express high levels of intracellular MUCL1. MUCL1 expression is highest in HER2-amplified breast tumors and inhibiting HER2 activity in tumor cells resulted in a decreased MUCL1 expression. In-depth investigation demonstrated that phosphoinositide3-kinase/Akt pathway, but not Ras/MEK pathway, controls MUCL1 expression downstream of HER2. Phenotypic assays revealed a strong dependence of HER2-positive cells on MUCL1 for cell proliferation. We further identified the mechanism by which MUCL1 regulates cell growth. Knockdown of MUCL1 induced a G1/S phase arrest concomitant with decreased cyclin D and increased p21 and p27 levels. Finally, we investigated the impact of MUCL1 loss on kinase signaling pathways in breast cancer cells through phospho-kinase array profiling. MUCL1 silencing abrogated phospho-focal adhesion kinase (FAK), Jun NH2-terminal kinase (JNK) and c-Jun signals, but not extracellular signal-regulated kinase or Akt pathway activities, thereby pointing to FAK/JNK pathway as the downstream effector of MUCL1 signaling. We are the first to identify an important role for MUCL1 in the proliferation of breast cancer cells, probably mediated via the FAK/JNK signaling pathway. Taken together, these data suggest a potential utility for therapeutic targeting of this protein in breast cancer.

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Section: Introductionmentioning

confidence: 99%

HER2 drives Mucin-like 1 to control proliferation in breast cancer cells

Conley¹,

Bosco²,

Tice³

et al. 2016

Oncogene

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“…So, we examined SBEM levels in FFPE tissue sections by IHC test and then analyzed the correlation of SBEM expression with DFS and OS. Liu et al reported that SBEM protein expression correlated with tumor size, TNM staging and lymph node metastasis [9]. Ki67 is used to assess the prognosis of cancer patients [23].…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, SBEM expression in PB (Peripheral blood) of breast cancer patients was markedly higher than that of healthy donors and other cancer patients [9]. Determination of SBEM protein in tissue and mRNA expression in PB of TNBC patients maybe helpful for early diagnosis, choice of treatment, decision of the degree of malignancy and risk prediction of recurrence.…”

Section: Discussionmentioning

confidence: 99%

“…High SBEM expression was found to be strongly associated with the histopathological detection of lymph node metastases [7]. Several laboratories showed that SBEM expression correlated with higher tumor grade [8], TNM staging and lymph node metastasis at both mRNA and protein levels [9]. SBEM protein was more frequently observed in ER- than in ER + breast cancers [8,10] and SBEM expression showed a trend towards an association with decreased OS and DFS in SBEM + patients [8].…”

Section: Introductionmentioning

confidence: 99%

“…Valladares Ayerbes et al [10] studied the expression profiles of SBEM gene in silico and in vitro, and demonstrated that SBEM-mRNA could serve as a marker for bone marrow micro metastasis in breast cancer patients [10]. Researchers also reported that SBEM had the potential to be a specific marker for predicting hematogenous micro metastasis and responses to neo-adjuvant chemotherapy in breast cancer [9]. …”

Section: Introductionmentioning

confidence: 99%

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Small breast epithelial mucin tumor tissue expression is associated with increased risk of recurrence and death in triple-negative breast cancer patients

Liu

et al. 2013

Diagn Pathol

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BackgroundSmall breast epithelial mucin (SBEM) has been implicated in tumor genesis and micrometastasis in breast cancer. Triple-negative breast cancer (TNBC) was characterized by high incidence in young women,early relapse and a very poor prognosis. The aim of this study was to evaluate the association of SBEM expression in tissues of TNBC with disease-free survival (DFS) and overall survival (OS).MethodsSBEM protein expression was detected in 87 available formalin-fixed paraffin-embedded (FFPE) tissue specimens from TNBC patients by means of immunohistochemistry (IHC). We analyzed the correlation between the SBEM protein expression and DFS and OS during a 5 year follow-up period, respectively. And a SBEM cut-off value of prognosis was established associated with DFS and OS. SBEM was analyzed against other risk factors in multivariate analysis.ResultsSBEM 3+ score was cut-off value of prognosis and significantly correlated with DFS (p = 0.000) and OS (p = 0.001) in TNBC patients. There was a marked associations (p <0.05) between SBEM 3+ score and tumor size, grade, node status, TNM stage and Ki67. Multivariate analysis showed that patients with SBEM 3+ represented a higher risk of recurrence and mortality than those with a lower SBEM expression (HR = 3.370 with p = 0.008 for DFS and HR = 4.185 with p = 0.004 for OS).ConclusionsSBEM is an independent risk predictor and may offer utility as a prognostic marker in TNBC patients.Virtual Slideshttp://www.diagnosticpathology.diagnomx.eu/vs/1624613061936917

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Detailed role of microRNA‐mediated regulation of PI3K/AKT axis in human tumors

Al‐Hawary,

Ruzibakieva,

Gupta

et al. 2023

Cell Biochemistry & Function

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The regulation of signal transmission and biological processes, such as cell proliferation, apoptosis, metabolism, migration, and angiogenesis are greatly influenced by the PI3K/AKT signaling pathway. Highly conserved endogenous non‐protein‐coding RNAs known as microRNAs (miRNAs) have the ability to regulate gene expression by inhibiting mRNA translation or mRNA degradation. MiRNAs serve key role in PI3K/AKT pathway as upstream or downstream target, and aberrant activation of this pathway contributes to the development of cancers. A growing body of research shows that miRNAs can control the PI3K/AKT pathway to control the biological processes within cells. The expression of genes linked to cancers can be controlled by the miRNA/PI3K/AKT axis, which in turn controls the development of cancer. There is also a strong correlation between the expression of miRNAs linked to the PI3K/AKT pathway and numerous clinical traits. Moreover, PI3K/AKT pathway‐associated miRNAs are potential biomarkers for cancer diagnosis, therapy, and prognostic evaluation. The role and clinical applications of the PI3K/AKT pathway and miRNA/PI3K/AKT axis in the emergence of cancers are reviewed in this article.

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Small breast epithelial mucin (SBEM) has the potential to be a marker for predicting hematogenous micrometastasis and response to neoadjuvant chemotherapy in breast cancer

Cited by 18 publications

References 30 publications

HER2 drives Mucin-like 1 to control proliferation in breast cancer cells

HER2 drives Mucin-like 1 to control proliferation in breast cancer cells

Small breast epithelial mucin tumor tissue expression is associated with increased risk of recurrence and death in triple-negative breast cancer patients

Detailed role of microRNA‐mediated regulation of PI3K/AKT axis in human tumors

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