CCL5 increases lung cancer migration via PI3K, Akt and NF-κB pathways

Huang, Chun‐Yin; Fong, Yi‐Chin; Lee, Chun-Yi; Chen, Mengyi; Tsai, Hsiao‐Chi; Hsu, Horng‐Chaung; Tang, Chih-Hsin

doi:10.1016/j.bcp.2008.11.014

Cited by 160 publications

(118 citation statements)

References 40 publications

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“…The PI3K/Akt signaling pathway plays a vital role in the regulation of numerous cellular functions, including tumor progression, angiogenesis, adhesion, migration, survival and drug resistance, in many human cancers (31) and is involved in cisplatin-based chemotherapy resistance in epithelial ovarian cancer (32). In addition, the Akt signaling pathway can be activated via chemokines or cytokines, such as CCL5 (19,33,34). We hypothesized that these two pathways were involved in the regulation of cisplatin resistance by CCL5.…”

Section: Ccl5 Stimulation Promotes Cisplatin Resistance Of Ovarian Camentioning

confidence: 99%

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Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways

Zhou

Sun

et al. 2016

International Journal of Oncology

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Abstract. Currently, acquired resistance to cisplatin (DDP) is a substantial obstacle to reducing the morbidity and mortality due to ovarian malignant tumors. Nevertheless, cisplatin plays a vital role in killing the tumor cells while it may also be a 'primer' involved in chemotherapy resistance. We found that the cisplatin-induced chemokine (C-C motif) ligand 5 (CCL5) secretion derived from cancer-associated fibroblasts (CAFs) promoted ovarian cancer cell resistance to cisplatin. Via a cytokine chip assay, we identified a spectrum of secreted proteins that were derived from the CAFs through cisplatin-induced treatment. Among these, CCL5 significantly attenuated the cytotoxic effect of cisplatin chemotherapy in vitro and in vivo. Additionally, CCL5 expression was also detected in 62 serous ovarian cancer patient tissue specimens using IHC, and the results demonstrated that chemotherapy resistant patients displayed higher expression of CCL5 than the chemo-sensitive patients (P<0.05). Mechanistically, we found that CCL5 notably increased STAT3 and Akt phosphorylation levels in ovarian cancer cells. These results indicated that cisplatininduced CCL5 secretion derived from the CAFs may promote cisplatin resistance, which was mediated by regulation of the STAT3 and PI3K/Akt signal pathways.

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Section: Ccl5 Stimulation Promotes Cisplatin Resistance Of Ovarian Camentioning

confidence: 99%

“…Moreover, the STAT3-CCL5 signaling pathway has been shown to play an important role in tamoxifen resistance in human breast cancer cells (3). The PI3K/Akt signaling pathway also plays a lead role in tumor progression and chemotherapy resistance and this signaling pathway can be activated by CCL5 (19).…”

Section: Introductionmentioning

confidence: 99%

Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways

Zhou

Sun

et al. 2016

International Journal of Oncology

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“…RANTES has been detected in samples from patients with breast cancer, and its expression was correlated with disease progression (23,42,43). Positive feedback between STAT3 and RANTES may increase the aggressiveness of TRM-7 cells.…”

Section: Rantes and Stat3 Blockade Inhibits Drug Resistance In Trm-7 mentioning

confidence: 99%

“…Associations between RANTES expression and melanoma, lung, prostate, and pancreatic cancers have been reported (23)(24)(25). In terms of breast cancer, a number of studies have suggested that RANTES is associated with breast malignancy.…”

Section: Introductionmentioning

confidence: 99%

STAT3-RANTES Autocrine Signaling Is Essential for Tamoxifen Resistance in Human Breast Cancer Cells

Lee

et al. 2013

Molecular Cancer Research

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The acquisition of tamoxifen resistance is a major therapeutic problem in breast cancer. We developed a tamoxifen-resistant MCF-7 (TRM-7) cell line to elucidate the molecular mechanisms and factors associated with acquisition of such resistance. We showed that phosphorylation of STAT3 at tyrosine 705 (Y705) and RANTES expression are increased in response to tamoxifen in human breast cancer cells. On the basis of these results, we hypothesize that upregulated STAT3 phosphorylation and RANTES may be correlated with the development of drug resistance. Here, we showed that STAT3 and RANTES contribute to the maintenance of drug resistance. STAT3 phosphorylation is constitutively retained via a RANTES autocrine loop, which in turn upregulates antiapoptotic signals in TRM-7 cells. STAT3-RANTES autocrine signaling affected expression of anti-apoptotic BCL-2 family genes and prevented TRM-7 cells from undergoing programmed cell death by inhibiting PARP and caspase-9 cleavage. Subsequently, blockade of STAT3 and RANTES in TRM-7 cells resulted in reduction of antiapoptotic signals, which was rescued by exogenous RANTES treatment; drug resistance was also restored. Taken together, our results suggested that STAT3-RANTES autocrine signaling is essential for maintenance of drug resistance and inhibition of programmed cell death. These mechanisms of STAT3-RANTES autocrine signaling suggest a novel strategy for management of patients with tamoxifen-resistant tumors. Mol Cancer Res; 11(1); 31-42. Ó2012 AACR. IntroductionBreast cancer is the second most common cancer worldwide after lung cancer, the fifth most common cause of cancer death, and the leading cause of cancer death in women. The global burden of breast cancer exceeds that of all other cancers, and its incidence is increasing (1). In women younger than 50 years with breast cancer, chemotherapy increases the 15-year survival rate by 10%,

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“…mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OSA cell lines, namely HOS/143B and SaOS-2/LM7 (Flores et al, 2012). CCL5 has been reported to stimulate directional migration and invasion of human cancer cells (Huang et al, 2009;Kulbe et al, 2004). CCL5 directed human OSA cell migration (U2OS and MG63 cells) .…”

Section: Mechanisms Of the Osa Metastasismentioning

confidence: 99%

Review of the Molecular Pathogenesis of Osteosarcoma

Hao²,

Wang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

124

109

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Treating the osteosarcoma (OSA) remains a challenge. Current strategies focus on the primary tumor and have limited efficacy for metastatic OSA. A better understanding of the OSA pathogenesis may provide a rational basis for innovative treatment strategies especially for metastases. The aim of this review is to give an overview of the molecular mechanisms of OSA tumorigenesis, OSA cell proliferation, apoptosis, migration, and chemotherapy resistance, and how improved understanding might contribute to designing a better treatment target for OSA.

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CCL5 increases lung cancer migration via PI3K, Akt and NF-κB pathways

Cited by 160 publications

References 40 publications

Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways

Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways

STAT3-RANTES Autocrine Signaling Is Essential for Tamoxifen Resistance in Human Breast Cancer Cells

Review of the Molecular Pathogenesis of Osteosarcoma

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