Protein kinase Cα suppresses the expression of STC1 in MDA-MB-231 breast cancer cells

Cornmark, Louise; Lønne, Gry Kalstad; Jögi, Annika; Larsson, Christer

doi:10.1007/s13277-011-0205-2

Cited by 8 publications

(11 citation statements)

References 42 publications

(48 reference statements)

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“…Hypoxia-induced genes make cells more tolerant to the unfavorable conditions in certain cancer cell lines (24,25). In accordance with studies in other cell lines (9,(26)(27)(28)(29), it was demonstrated that STC1 could be stimulated in hypoxic environments. However, the roles of STC1 under hypoxic conditions are inconsistent according to different cell types.…”

Section: Discussionsupporting

confidence: 77%

Stanniocalcin‑1 promotes cell proliferation, chemoresistance and metastasis in hypoxic gastric cancer cells via Bcl‑2

Wang

Zhou

et al. 2019

Oncol Rep

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Gastric cancer (GC) is one of the most lethal diseases worldwide, but the mechanism of GC development remains elusive. In the present study, the roles of stanniocalcin-1 (STC1) in GC were investigated. It was demonstrated that overexpression of STC1 mRNA and protein were associated with poor survival of patients with GC. The expression of STC1 was enhanced in hypoxic GC cells and overexpression of STC1 facilitated cell proliferation in hypoxia but not in normoxia. Furthermore, STC1 promoted chemoresistance, migration and invasion in hypoxia. Upregulating the expression of STC1 enhanced the expression of B cell lymphoma (Bcl)-2, neural-cadherin and matrix metalloproteinase-2, whereas it reduced the levels of cytochrome c, cleaved-caspase-9, cleaved-caspase-3 and epithelial-cadherin. However, downregulation of STC1 altered the expression of these proteins in the opposite direction. Furthermore, disturbing the expression of Bcl-2 partly reversed the changes to these proteins and also the pro-proliferation, anti-apoptosis and pro-invasion potential of STC1. In vivo experiments indicated that enhanced expression of STC1 promoted tumor growth and metastasis in mice. Collectively, the results indicated that STC1 may serve an oncogenic role in hypoxic GC via dysregulating Bcl-2, indicating that STC1 may be a potential therapeutic target in the treatment of GC.

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Section: Discussionsupporting

confidence: 77%

Stanniocalcin‑1 promotes cell proliferation, chemoresistance and metastasis in hypoxic gastric cancer cells via Bcl‑2

Wang

Zhou

et al. 2019

Oncol Rep

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“…Although most of studies have focused on the calcium-regulating functions of STC1, increasing evidence suggests that STC1 may also play a major role in carcinoma. High expression of STC1 was frequently detected in human tumor samples of hepatocellular carcinoma (HCC) [16], colorectal cancer [17], lung adenocarcinoma [9], breast cancer [18, 19] and thyroid carcinomas [20], however, low expression of STC1 was found in tumor-derived ovarian epithelial cells [21]. Our previous studies have shown that STC1 is on the decrease in cervical cancer cells for the first time, and that it suppresses cellular multiplication and metastasis of cervical cancer cells likely through NF-κB P65 protein [22].…”

Section: Introductionmentioning

confidence: 99%

STC1 promotes cell apoptosis via NF-κB phospho-P65 Ser536 in cervical cancer cells

Jiang

Liu

et al. 2017

Oncotarget

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Stanniocalin-1 (STC1) is a secreted glycoprotein hormone and involved in various types of human malignancies. Our previous studies revealed that STC1 inhibited cell proliferation and invasion of cervical cancer cells through NF-κB P65 activation, but the mechanism is poorly understood. In our studies, we found overexpression of STC1 promoted cell apoptosis while silencing of STC1 promoted cell growth of cervical cancer. Phospho-protein profiling and Western blotting results showed the expression of NF-κB related phosphorylation sites including NF-κB P65 (Ser536), IκBα, IKKβ, PI3K, and AKT was altered in STC1-overexpressed cervical cancer cells. Moreover, PI3K inhibitor LY294002, AKT-shRNA and IκBα-shRNA could decrease the protein content of phospho-P65 (Ser536), phospho-IκBα, phospho-AKT and phospho-IKKβ while increasing the level of P65 compared to STC1 overexpression groups in cervical cancer cells. Also, PI3K inhibitor LY294002, AKT-shRNA and IκBα-shRNA elevated the percentage of apoptosis and suppressed the G1/S transition in those cells. Additionally, STC1 level was decreased in cervical cancer, especial in stage II and III. The results of immunohistochemistry for the cervical cancer microarray showed that a lower level of STC1, phospho-PI3K and P65 protein expression in tumor tissues than that in normal tissues, and a higher level of phospho-P65 protein expression in tumor tissues, which is consistent with the results of the Western blotting. These data demonstrated that STC1 can promote cell apoptosis via NF-κB phospho-P65 (Ser536) by PI3K/AKT, IκBα and IKK signaling in cervical cancer cells. Our results offer the first mechanism that explains the link between STC1 and cell apoptosis in cervical cancer.

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“…Western blot was performed as described in a previous publication [ 37 ]. Primary antibodies used were anti-PKCδ (1:500, Santa Cruz), anti-Smac (1:500, Santa Cruz), anti-Actin (1:2000, MP Biomedicals), anti-HSV (1:1000, Novagen), anti-GST (1:2000, GE Healthcare) and anti-GFP (1:1000, Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

Molecular characterization of protein kinase C delta (PKCδ)-Smac interactions

et al. 2016

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BackgroundProtein kinase C δ (PKCδ) is known to be an important regulator of apoptosis, having mainly pro- but also anti-apoptotic effects depending on context. In a previous study, we found that PKCδ interacts with the pro-apoptotic protein Smac. Smac facilitates apoptosis by suppressing inhibitor of apoptosis proteins (IAPs). We previously established that the PKCδ-Smac complex dissociates during induction of apoptosis indicating a functional importance. Because the knowledge on the molecular determinants of the interaction is limited, we aimed at characterizing the interactions between PKCδ and Smac.ResultsWe found that PKCδ binds directly to Smac through its regulatory domain. The interaction is enhanced by the PKC activator TPA and seems to be independent of PKCδ catalytic activity since the PKC kinase inhibitor GF109203X did not inhibit the interaction. In addition, we found that C1 and C2 domains from several PKC isoforms have Smac-binding capacity.ConclusionsOur data demonstrate that the Smac-PKCδ interaction is direct and that it is facilitated by an open conformation of PKCδ. The binding is mediated via the PKCδ regulatory domain and both the C1 and C2 domains have Smac-binding capacity. With this study we thereby provide molecular information on an interaction between two apoptosis-regulating proteins.

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Protein kinase Cα suppresses the expression of STC1 in MDA-MB-231 breast cancer cells

Cited by 8 publications

References 42 publications

Stanniocalcin‑1 promotes cell proliferation, chemoresistance and metastasis in hypoxic gastric cancer cells via Bcl‑2

Stanniocalcin‑1 promotes cell proliferation, chemoresistance and metastasis in hypoxic gastric cancer cells via Bcl‑2

STC1 promotes cell apoptosis via NF-κB phospho-P65 Ser536 in cervical cancer cells

Molecular characterization of protein kinase C delta (PKCδ)-Smac interactions

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