S-phase kinase-associated protein 2 expression interference inhibits breast cancer cell proliferation

Sun, Yi-Chih; Xk, Wang; Bj, Li

doi:10.4238/2015.august.10.4

Cited by 5 publications

(4 citation statements)

References 27 publications

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“…Overexpression of Skp2 is associated with poor prognosis in breast cancer [23, 26]. Moreover, overexpression of Skp2 promoted cell proliferation in breast cancer cells [26], whereas inhibition of Skp2 suppressed cell proliferation in MDA-MB-231 cells [27]. In line with this, we observed the similar results, suggesting that Skp2 contributes to breast cancer cell growth.…”

Section: Discussionsupporting

confidence: 82%

Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells

Yin

Hou

et al. 2016

Oncotarget

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Studies have investigated the tumor suppressive role of rottlerin in carcinogenesis. However, the molecular mechanisms of rottlerin-induced anti-tumor activity are largely unclear. Skp2 (S-phase kinase associated protein 2) has been validated to play an oncogenic role in a variety of human malignancies. Therefore, inactivation of Skp2 could be helpful for the treatment of human cancers. In the current study, we explore whether rottlerin could inhibit Skp2 expression, leading to inhibition of cell growth, migration and invasion in breast cancer cells. We found that rottlerin treatment inhibited cell growth, induced apoptosis and cell cycle arrest. We also revealed that rottlerin suppressed cell migration and invasion in breast cancer cells. Mechanically, we observed that rottlerin significantly down-regulated the expression of Skp2 in breast cancer cells. Importantly, overexpression of Skp2 abrogated rottlerin-mediated tumor suppressive activity, whereas down-regulation of Skp2 enhanced rottlerin-triggered anti-tumor function. Strikingly, we identified that rottlerin exhibited its anti-tumor potential partly through inactivation of Skp2 in breast cancer. Our findings indicate that rottlerin could be a potential safe agent for the treatment of breast cancer.

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Section: Discussionsupporting

confidence: 82%

Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells

Yin

Hou

et al. 2016

Oncotarget

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“…Sun et al also reported that Skp2 expression is significantly higher in patients with invasive breast cancer than in normal breasts. 25 Our data also showed that high Skp2 expression positively correlated with reduced overall survival (OS), distant metastasis-free survival (DFS), relapse-free survival (RFS) and post-progression survival (PPS), suggesting a prognostic value of Skp2 in breast cancers. We also investigated the role of Skp2 and Skp2B in breast cancer cell growth, apoptosis and cell cycle arrest.…”

Section: Discussionsupporting

confidence: 62%

Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation

et al. 2016

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The F box protein Skp2 is oncogenic. Skp2 and Skp2B, an isoform of Skp2 are overexpressed in breast cancer. However, little is known regarding the mechanism by which Skp2B promotes the occurrence and development of breast cancer. Here, we determined the expression and clinical outcomes of Skp2 in breast cancer samples and cell lines using breast cancer database, and investigated the role of Skp2 and Skp2B in breast cancer cell growth, apoptosis and cell cycle arrest. We obtained Skp2 is significantly overexpressed in breast cancer samples and cell lines, and high Skp2 expression positively correlated with poor prognosis of breast cancer. Both Skp2 and Skp2B could promote breast cancer cell proliferation, inhibit cell apoptosis, change the cell cycle distribution and induce the increased S phase cells and therefore induce cell proliferation in breast cancer cells. Moreover, the 2 isoforms could both suppress PIG3 expression via independent pathways in the breast cancer cells. Skp2 suppressed p53 and inhibited PIG3-induced apoptosis, while Skp2B attenuated the function of PIG3 by inhibiting PHB. Our results indicate that Skp2 and Skp2B induce breast cancer cell development and progression, making Skp2 and Skp2B potential molecular targets for breast cancer therapy.

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“…Moreover, SKP2 silence significantly reduced breast cancer cell MDA-MB-231 proliferation. This study could be the experimental basis for further investigation and potential clinical application [113].…”

Section: Skp2 Inhibitorsmentioning

confidence: 87%

Review of the Ubiquitin Role in DNA Repair and Tumorigenesis, with Emphasis in Breast Cancer Treatment; Current Data and Future Options

Mourtzoukou¹,

Drikos²,

Goutas³

et al. 2018

Ubiquitination Governing DNA Repair - Implications in Health and Disease

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Breast carcinoma remains the commonest carcinoma among women worldwide. Despite the fact that impressive progression has been achieved so far regarding pathophysiology, histopathology and treatment of this cancer, there are still undiscovered fields on molecular and therapeutic levels. The need of resolving problems such as chemoresistance, recurrence and metastasis has led in revealing key molecules in the development and progression of malignancies, including breast tumors. In this review, we will briefly describe the functions of ubiquitin and post-translational modifications (PTMs) focusing specially in DNA repair and then discuss about the implication of ubiquitin and related molecules in tumorigenesis and specifically in breast carcinoma. So far there are only few drugs approved by FDA that target the ubiquitin system. There will be an analysis regarding the current and potential anti-cancer therapeutic strategies based on targeting specific ubiquitin-related molecules.

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S-phase kinase-associated protein 2 expression interference inhibits breast cancer cell proliferation

Cited by 5 publications

References 27 publications

Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells

Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells

Skp2 is over-expressed in breast cancer and promotes breast cancer cell proliferation

Review of the Ubiquitin Role in DNA Repair and Tumorigenesis, with Emphasis in Breast Cancer Treatment; Current Data and Future Options

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