E1A-Mediated Inhibition of HSPA5 Suppresses Cell Migration and Invasion in Triple-Negative Breast Cancer

Hsin-An Chen, Yi Wen Chang, Chi Feng Tseng, C. F. Chiu, Chih Chen Hong, Weu Wang, Ming Yang Wang, Michael Hsiao, Jui Ti Ma, Chung Hsing Chen, Shih Sheng Jiang, Chih-Hsiung Wu, Mien Chie Hung, Ming-Te Huang, Jen Liang Su

Research output: Contribution to journalArticle

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Abstract

Background: Triple-negative breast cancer (TNBC) is defined by reduced expression of the estrogen receptor, progesterone receptor, and HER2. TNBC is an especially aggressive group of breast cancers with poor prognosis. There are currently no validated molecular targets to effectively treat this disease. Thus, it is necessary to identify effective molecular targets and therapeutic strategies for TNBC patients.

Methods: The expression of HSPA5 in patients with breast cancer was examined by immunohistochemistry. The association of HSPA5 expression with tumor grade and metastatic events in TNBC patients was analyzed using the Oncomine database. The knockdown and overexpression of HSPA5 protein were performed to investigate the effects on E1A-suppressed cell migration/invasion of TNBC using in vitro transwell assays and tumor growth/experimental metastasis studies in animal models.

Results: The expression of HSPA5 was positively correlated with high-grade tumors, metastatic events, and poor overall survival in breast cancer patients with TNBC. E1A-inhibited HSPA5 expression suppressed cell migration/invasive ability of TNBC cell lines. Moreover, E1A significantly abolished lung metastases from breast cancer cells by inhibiting HSPA5 expression in a xenograft tumor model.

Conclusions: The overexpression of HSPA5 is critical for high-risk metastasis of breast cancer and TNBC. The results of our study suggest that HSPA5 may be a crucial mediator of E1A-suppressed metastatic ability of breast cancer cells. Thus, E1A may be a potential target for diagnosis and individualized treatment in clinical practice.

Original languageEnglish
Pages (from-to)889-898
Number of pages10
JournalAnnals of Surgical Oncology
Volume22
Issue number3
DOIs
Publication statusPublished - 2015

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Triple Negative Breast Neoplasms
Cell Movement
Breast Neoplasms
Neoplasm Metastasis
Neoplasms
Progesterone Receptors
Heterografts
Estrogen Receptors
Animal Models
Immunohistochemistry
Databases
Cell Line
Lung
Survival

ASJC Scopus subject areas

  • Surgery
  • Oncology
  • Medicine(all)

Cite this

E1A-Mediated Inhibition of HSPA5 Suppresses Cell Migration and Invasion in Triple-Negative Breast Cancer. / Chen, Hsin-An; Chang, Yi Wen; Tseng, Chi Feng; Chiu, C. F.; Hong, Chih Chen; Wang, Weu; Wang, Ming Yang; Hsiao, Michael; Ma, Jui Ti; Chen, Chung Hsing; Jiang, Shih Sheng; Wu, Chih-Hsiung; Hung, Mien Chie; Huang, Ming-Te; Su, Jen Liang.

In: Annals of Surgical Oncology, Vol. 22, No. 3, 2015, p. 889-898.

Research output: Contribution to journalArticle

Chen, H-A, Chang, YW, Tseng, CF, Chiu, CF, Hong, CC, Wang, W, Wang, MY, Hsiao, M, Ma, JT, Chen, CH, Jiang, SS, Wu, C-H, Hung, MC, Huang, M-T & Su, JL 2015, 'E1A-Mediated Inhibition of HSPA5 Suppresses Cell Migration and Invasion in Triple-Negative Breast Cancer', Annals of Surgical Oncology, vol. 22, no. 3, pp. 889-898. https://doi.org/10.1245/s10434-014-4061-3
Chen, Hsin-An ; Chang, Yi Wen ; Tseng, Chi Feng ; Chiu, C. F. ; Hong, Chih Chen ; Wang, Weu ; Wang, Ming Yang ; Hsiao, Michael ; Ma, Jui Ti ; Chen, Chung Hsing ; Jiang, Shih Sheng ; Wu, Chih-Hsiung ; Hung, Mien Chie ; Huang, Ming-Te ; Su, Jen Liang. / E1A-Mediated Inhibition of HSPA5 Suppresses Cell Migration and Invasion in Triple-Negative Breast Cancer. In: Annals of Surgical Oncology. 2015 ; Vol. 22, No. 3. pp. 889-898.
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abstract = "Background: Triple-negative breast cancer (TNBC) is defined by reduced expression of the estrogen receptor, progesterone receptor, and HER2. TNBC is an especially aggressive group of breast cancers with poor prognosis. There are currently no validated molecular targets to effectively treat this disease. Thus, it is necessary to identify effective molecular targets and therapeutic strategies for TNBC patients.Methods: The expression of HSPA5 in patients with breast cancer was examined by immunohistochemistry. The association of HSPA5 expression with tumor grade and metastatic events in TNBC patients was analyzed using the Oncomine database. The knockdown and overexpression of HSPA5 protein were performed to investigate the effects on E1A-suppressed cell migration/invasion of TNBC using in vitro transwell assays and tumor growth/experimental metastasis studies in animal models.Results: The expression of HSPA5 was positively correlated with high-grade tumors, metastatic events, and poor overall survival in breast cancer patients with TNBC. E1A-inhibited HSPA5 expression suppressed cell migration/invasive ability of TNBC cell lines. Moreover, E1A significantly abolished lung metastases from breast cancer cells by inhibiting HSPA5 expression in a xenograft tumor model.Conclusions: The overexpression of HSPA5 is critical for high-risk metastasis of breast cancer and TNBC. The results of our study suggest that HSPA5 may be a crucial mediator of E1A-suppressed metastatic ability of breast cancer cells. Thus, E1A may be a potential target for diagnosis and individualized treatment in clinical practice.",
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AU - Chen, Hsin-An

AU - Chang, Yi Wen

AU - Tseng, Chi Feng

AU - Chiu, C. F.

AU - Hong, Chih Chen

AU - Wang, Weu

AU - Wang, Ming Yang

AU - Hsiao, Michael

AU - Ma, Jui Ti

AU - Chen, Chung Hsing

AU - Jiang, Shih Sheng

AU - Wu, Chih-Hsiung

AU - Hung, Mien Chie

AU - Huang, Ming-Te

AU - Su, Jen Liang

PY - 2015

Y1 - 2015

N2 - Background: Triple-negative breast cancer (TNBC) is defined by reduced expression of the estrogen receptor, progesterone receptor, and HER2. TNBC is an especially aggressive group of breast cancers with poor prognosis. There are currently no validated molecular targets to effectively treat this disease. Thus, it is necessary to identify effective molecular targets and therapeutic strategies for TNBC patients.Methods: The expression of HSPA5 in patients with breast cancer was examined by immunohistochemistry. The association of HSPA5 expression with tumor grade and metastatic events in TNBC patients was analyzed using the Oncomine database. The knockdown and overexpression of HSPA5 protein were performed to investigate the effects on E1A-suppressed cell migration/invasion of TNBC using in vitro transwell assays and tumor growth/experimental metastasis studies in animal models.Results: The expression of HSPA5 was positively correlated with high-grade tumors, metastatic events, and poor overall survival in breast cancer patients with TNBC. E1A-inhibited HSPA5 expression suppressed cell migration/invasive ability of TNBC cell lines. Moreover, E1A significantly abolished lung metastases from breast cancer cells by inhibiting HSPA5 expression in a xenograft tumor model.Conclusions: The overexpression of HSPA5 is critical for high-risk metastasis of breast cancer and TNBC. The results of our study suggest that HSPA5 may be a crucial mediator of E1A-suppressed metastatic ability of breast cancer cells. Thus, E1A may be a potential target for diagnosis and individualized treatment in clinical practice.

AB - Background: Triple-negative breast cancer (TNBC) is defined by reduced expression of the estrogen receptor, progesterone receptor, and HER2. TNBC is an especially aggressive group of breast cancers with poor prognosis. There are currently no validated molecular targets to effectively treat this disease. Thus, it is necessary to identify effective molecular targets and therapeutic strategies for TNBC patients.Methods: The expression of HSPA5 in patients with breast cancer was examined by immunohistochemistry. The association of HSPA5 expression with tumor grade and metastatic events in TNBC patients was analyzed using the Oncomine database. The knockdown and overexpression of HSPA5 protein were performed to investigate the effects on E1A-suppressed cell migration/invasion of TNBC using in vitro transwell assays and tumor growth/experimental metastasis studies in animal models.Results: The expression of HSPA5 was positively correlated with high-grade tumors, metastatic events, and poor overall survival in breast cancer patients with TNBC. E1A-inhibited HSPA5 expression suppressed cell migration/invasive ability of TNBC cell lines. Moreover, E1A significantly abolished lung metastases from breast cancer cells by inhibiting HSPA5 expression in a xenograft tumor model.Conclusions: The overexpression of HSPA5 is critical for high-risk metastasis of breast cancer and TNBC. The results of our study suggest that HSPA5 may be a crucial mediator of E1A-suppressed metastatic ability of breast cancer cells. Thus, E1A may be a potential target for diagnosis and individualized treatment in clinical practice.

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