Gene expression profiling combined with functional analysis identify integrin beta1 (ITGB1) as a potential prognosis biomarker in triple negative breast cancer

Klahan, Sukhontip; Huang, Wan-Chen; Chang, Che Mai; Wong, Henry Sung Ching; Huang, Chi Cheng; Wu, Mei; Lin, Yu Chiao; Lu, Hsing Fang; Hou, Ming‐Feng; Chang, Wei Chiao

doi:10.1016/j.phrs.2015.12.004

Cited by 44 publications

(29 citation statements)

References 33 publications

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“…Interestingly, previous evidence demonstrated that expressions of ER and PR were not correlated with expression of β1-integrin in clinical outcomes [ 39 ]. Consistent with this finding, Klahan et al colleagues combined microarray data from two databases and suggested that β1 integrin is a potential candidate biomarker of TNBC patients [ 40 ]. Therefore, we next investigated clarification of the role of β1 integrin in TNBC patients.…”

Section: Discussionmentioning

confidence: 89%

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β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer

Yin

Lin

et al. 2016

IJMS

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Triple negative breast cancer (TNBC) displays higher risk of recurrence and distant metastasis. Due to absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), TNBC lacks clinically established targeted therapies. Therefore, understanding of the mechanism underlying the aggressive behaviors of TNBC is required for the design of individualized strategies and the elongation of overall survival duration. Here, we supported a positive correlation between β1 integrin and malignant behaviors such as cell migration, invasion, and drug resistance. We found that silencing of β1 integrin inhibited cell migration, invasion, and increased the sensitivity to anti-cancer drug. In contrast, activation of β1 integrin increased cell migration, invasion, and decreased the sensitivity to anti-cancer drug. Furthermore, we found that silencing of β1 integrin abolished Focal adhesion kinese (FAK) mediated cell survival. Overexpression of FAK could restore cisplatin-induced apoptosis in β1 integrin-depleted cells. Consistent to in vitro data, β1 integrin expression was also positively correlated with FAK (p = 0.031) in clinical tissue. More importantly, β1 integrin expression was significantly correlated with patient outcome. In summary, our study indicated that β1 integrin could regulate TNBC cells migration, invasion, drug sensitivity, and be a potential prognostic biomarker in TNBC patient survival.

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Section: Discussionmentioning

confidence: 89%

“…Cell invasion assay were performed as previously described [ 40 ]. In brief, cells were seeded in the inserts placed in the upper chamber of transwell.…”

Section: Methodsmentioning

confidence: 99%

β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer

Yin

Lin

et al. 2016

IJMS

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“…56 (iii) ITGB-1: Increasing evidence suggests that ITGB-1 is a potential molecular therapeutic target in BC. 57,58 The therapeutic potential of targeting ITGB-1 using various strategies or inhibitors, such as monoclonal antibodies, peptides, or synthetic peptides, and siRNA is being investigated. Inhibitors that silence ITGB-1 were shown to suppress tumor progression and metastasis in vitro and in vivo.…”

Section: 3mentioning

confidence: 99%

<p>HIF-1α, TWIST-1 and ITGB-1, associated with Tumor Stiffness, as Novel Predictive Markers for the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer</p>

Zhang

Gao

et al. 2020

CMAR

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Purpose: To investigate the relationship between hypoxia-inducible factor 1-alpha (HIF-1α), Twist family BHLH transcription factor 1 (TWIST-1), and β1 integrin (ITGB-1) expression and tumor stiffness, and evaluate performance of HIF-1α, TWIST-1, and ITGB-1 alone and in combination with Ki-67 for predicting pathological responses to neoadjuvant chemotherapy (NACT) in breast cancer (BC). Patients and Methods: This was a prospective cohort study of 104 BC patients receiving NACT. Tumor stiffness and oxygen score (OS) were evaluated before NACT by shear-wave elastography and optical imaging; HIF-1α, TWIST-1, ITGB-1, and Ki-67 expression were quantitatively assessed by immunohistochemistry of paraffin-embedded tumor samples obtained by core needle biopsy. Indexes were compared among different residual cancer burden (RCB) groups, and associations of HIF-1α, TWIST-1, ITGB-1, and Ki-67 with tumor stiffness and OS were examined. The value of HIF-1α, TWIST-1, ITGB-1, and Ki-67, and a possible new combined index (predRCB) for predicting NACT responses was assessed by receiver operating characteristic (ROC) curves. Results: HIF-1α, TWIST-1, and ITGB-1 expression were positively correlated with tumor stiffness and negatively with OS. Area under the ROC curves (AUCs) measuring the performance of HIF-1α, TWIST-1, ITGB-1, and Ki-67 for predicting responses to NACT were 0.81, 0.85, 0.79, and 0.80 for favorable responses, and 0.83, 0.86, 0.84, and 0.85 for resistant responses, respectively. PredRCB showed better prediction than the other individual indexes for favorable responses (AUC = 0.88) and resistant responses (AUC = 0.92). Conclusion: HIF-1α, TWIST-1, ITGB-1, and Ki-67 performed well in predicting favorable responses and resistance to NACT, and predRCB improved the predictive power of the individual indexes. These results support individualized treatment of BC patients receiving NACT.

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“…Moreover, its aberrant expression in cancer promotes cell motility and invasiveness (Guo, Lee, Kamar, Akiyama, & Pierce, ; Liu et al, ). In breast cancer, β1 integrin is overexpressed and is associated with a poor prognosis (Huck, Pontier, Zuo, & Muller, ; Klahan et al, ). Moreover, its silencing inhibits MDA‐MB‐231 cell migration, invasion, and store‐operated calcium influx (Klahan et al, ).…”

Section: Introductionmentioning

confidence: 99%

sp²‐Iminosugar α‐glucosidase inhibitor 1‐C‐octyl‐2‐oxa‐3‐oxocastanospermine specifically affected breast cancer cell migration through Stim1, β1‐integrin, and FAK signaling pathways

Gueder¹,

Allan²,

Telliez³

et al. 2017

Journal Cellular Physiology

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Aberrant glycosylation changes on many glycoproteins are often related to cancer progression and metastasis. sp -Iminosugar-type castanospermine analogues, inhibitors of α-glucosidases, have been reported to exhibit antitumor activity. However, their effects on cell migration and the underlying molecular mechanism are not fully understood. Here, we investigated the effect of the pseudo-C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives (CO-OCS) on breast cancer cells (MCF-7 and MDA-MB-231 cells), and MCF-10A mammary normal cell lines. We showed that CO-OCS treatment results in the drastic decrease of breast cancer cell migration without affecting cell proliferation. Furthermore, CO-OCS significantly reduced both the expression of β1-integrin, which is a crucial interacting partner of Focal Adhesion Kinase (FAK), and the phosphorylation rates of FAK and ERK1/2. CO-OCS also drastically reduced Ca entry through Store Operated Channels (SOC). Orai1 and Stim1, two N-glycosylated proteins, are involved in Store-Operated Calcium Entry (SOCE), and are essential for breast tumor cell migration. Our results showed that CO-OCS decreased the expression, at the protein level, of Stim1 without affecting that of Orai1. Moreover, cell migration and SOCE were attenuated by CO-OCS as well as when Stim1 was silenced. In contrast, in MCF-10A cells, CO-OCS slightly reduced cell migration, but was without effect on gene expression of Stim1, Orai1, β1-integrin, or FAK and ERK1/2 activation. Our results provide strong evidence for a significant effect of CO-OCS on breast cancer cell migration and support that this effect was associated with β1-integrin, Stim1, and FAK signaling pathways.

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Gene expression profiling combined with functional analysis identify integrin beta1 (ITGB1) as a potential prognosis biomarker in triple negative breast cancer

Cited by 44 publications

References 33 publications

β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer

β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer

<p>HIF-1α, TWIST-1 and ITGB-1, associated with Tumor Stiffness, as Novel Predictive Markers for the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer</p>

sp²‐Iminosugar α‐glucosidase inhibitor 1‐C‐octyl‐2‐oxa‐3‐oxocastanospermine specifically affected breast cancer cell migration through Stim1, β1‐integrin, and FAK signaling pathways

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Gene expression profiling combined with functional analysis identify integrin beta1 (ITGB1) as a potential prognosis biomarker in triple negative breast cancer

Cited by 44 publications

References 33 publications

β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer

β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer

<p>HIF-1α, TWIST-1 and ITGB-1, associated with Tumor Stiffness, as Novel Predictive Markers for the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer</p>

sp2‐Iminosugar α‐glucosidase inhibitor 1‐C‐octyl‐2‐oxa‐3‐oxocastanospermine specifically affected breast cancer cell migration through Stim1, β1‐integrin, and FAK signaling pathways

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sp²‐Iminosugar α‐glucosidase inhibitor 1‐C‐octyl‐2‐oxa‐3‐oxocastanospermine specifically affected breast cancer cell migration through Stim1, β1‐integrin, and FAK signaling pathways