RACK1 promotes the proliferation, migration and invasion capacity of mouse hepatocellular carcinoma cell line in vitro probably by PI3K/Rac1 signaling pathway

Wu, Jun; Meng, Jinyi; Du, Ye; Huang, Yühong; Jin, Yanling; Zhang, Jun; Wang, Bo; Zhang, Yuhong; Sun, Ming‐Zhong; Tang, Jianwu

doi:10.1016/j.biopha.2013.01.011

Cited by 40 publications

(33 citation statements)

References 31 publications

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“…Recent studies (27,29) have demonstrated that RACK1 plays a context-dependent role in tumorigenesis and is responsible for stress-mediated chemotherapy resistance. Our results demonstrated that RACK1 modulated sorafenib-induced apoptosis by regulating IRE1 activity, and the overexpression of RACK1 promoted the phosphorylation of IRE1 and inhibited apoptosis induced by sorafenib.…”

Section: Discussionmentioning

confidence: 99%

“…RACK1 can recruit and bind many kinases and receptors, such as PKC and DJ-1, thereby impacting a wide range of signal transduction pathways (24,25). RACK1 plays an important role in multiple cellular functions, including cell growth, migration and differentiation (26,27). Studies have found that RACK1 is upregulated in several tumor types, such as breast tumors and HCC (28,29).…”

Section: Introductionmentioning

confidence: 99%

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RACK1 modulates apoptosis induced by sorafenib in HCC cells by interfering with the IRE1/XBP1 axis

Zhou

Guo

et al. 2015

Oncology Reports

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Abstract. Sorafenib is one of the preferred drugs for the treatment of advanced primary hepatocellular carcinoma (HCC). However, its side-effects and acquired resistance limit its use. The unfolded protein response (UPR) induced by chemotherapeutics has been demonstrated to be required for tumor cells to maintain malignancy and therapy resistance. Activation of the IRE1/XBP1 pathway during the UPR is important for tumor survival under pathophysiological conditions. In the present study, we found that the UPR was activated and RACK1 was overexpressed in three human HCC cell lines and in HCC samples. Activation of the IRE1/XBP1 signaling pathway plays a protective role when HCC cells encounter endoplasmic reticulum (ER) stress due to in vitro sorafenib treatment. We then found that the interaction between IRE1 and RACK1 was essential for the activation of IRE1 signaling in sorafenibtreated cells. Exogenous overexpression of RACK1 enhanced the phosphorylation level of IRE1 and increased XBP1 mRNA splicing activity, which protected the HCC cells from sorafenib-induced apoptosis. However, the re-expression of RACK1 led HCC cells to regain susceptibility to sorafenibinduced apoptosis. Taken together, the present study suggests that the RACK1/IRE1 complex may contribute to activation of the UPR in HCC cells. Targeting RACK1 in combination with sorafenib administration is a potential strategy for clinical trials of advanced HCC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RACK1 modulates apoptosis induced by sorafenib in HCC cells by interfering with the IRE1/XBP1 axis

Zhou

Guo

et al. 2015

Oncology Reports

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“…Its overexpression in Hca-P, an initial (low) and specific lymph node metastasis (LNM) murine hepatocarcinoma cell line [2,4,[23][24][25][26][27][28], suppresses the in vitro proliferation, migration and invasion abilities of Hca-P cells. In current work, we continuously validated the potential tumor suppressor role of Our previous study (Biomed Pharmacother 2015;69:11) demonstrated that the over-expression of CRKL, a chicken tumor virus number 10 regulator of kinase-like protein, suppresses in vitro proliferation, invasion and migration of murine hepatocarcinoma Hca-P cell, a murine HCC cell with lymph node metastatic (LNM) rate of $25%.…”

Section: Introductionmentioning

confidence: 99%

CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells

Meng

Sun

Guo

et al. 2015

Biomedicine & Pharmacotherapy

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“…As a result, its dysregulation may contribute to tumorigenesis. In fact, RACK1 has been demonstrated to be involved in various types of malignant tumors including hepatocellular carcinoma, lung cancer, colon cancer, prostate cancer, cervical carcinoma, oral squamous cell carcinoma and neuroblastoma (13)(14)(15)(16)(17)(18)(19). However, whether RACK1 plays a role in malignant glioma as well as the mechanism involved remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Forced downregulation of RACK1 inhibits glioma development by suppressing Src/Akt signaling activity

Peng

Jiang

et al. 2013

Oncology Reports

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Abstract. Glioma is the most common primary brain malignant tumor. Receptor for activated C-kinase 1 (RACK1) is widely expressed in the central nervous system, and regulates multiple cellular processes including cell survival, proliferation, migration and metastasis. However, the role of RACK1 in glioma has never been revealed. The present study, for the first time, showed that RACK1 expression was significantly higher in glioma tissues and cell lines when compared with that in normal brain tissues, and was positively associated with the malignancy of glioma. siRNA-induced RACK1 downregulation significantly suppressed the proliferation and invasion of human glioma U87 and CHG-5 cells, while it promoted their apoptosis by upregulating Bax expression and reducing Bcl-2 expression. Furthermore, forced downregulation of RACK1 notably inhibited tumor xenograft growth in nude mice. These findings suggest that RACK1 plays a critical role in the development and progression of glioma in vitro and in vivo. Moreover, siRNA-induced RACK1 downregulation markedly reduced the activity of Src/Akt signaling pathway, which plays an important role in the growth and behavior of human malignancies, indicating that siRNA-mediated RACK1 downregulation inhibited glioma probably via suppressing Src/Akt signaling activity. The present study highlighted the role of RACK1 in glioma, and demonstrated that RACK1 is a novel promising therapeutic target for glioma treatment.

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RACK1 promotes the proliferation, migration and invasion capacity of mouse hepatocellular carcinoma cell line in vitro probably by PI3K/Rac1 signaling pathway

Cited by 40 publications

References 31 publications

RACK1 modulates apoptosis induced by sorafenib in HCC cells by interfering with the IRE1/XBP1 axis

RACK1 modulates apoptosis induced by sorafenib in HCC cells by interfering with the IRE1/XBP1 axis

CRKL knockdown promotes in vitro proliferation, migration and invasion, in vivo tumor malignancy and lymph node metastasis of murine hepatocarcinoma Hca-P cells

Forced downregulation of RACK1 inhibits glioma development by suppressing Src/Akt signaling activity

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