Galectin-1 Promotes Lung Cancer Progression and Chemoresistance by Upregulating p38 MAPK, ERK, and Cyclooxygenase-2

Chung, Ling Yen; Tang, Shanshan; Sun, Guang; Chou, Teh Ying; Yeh, Tien Shun; Yu, Sung-Liang; Sun, Kien-Wen

doi:10.1158/1078-0432.ccr-11-3348

Cited by 133 publications

(123 citation statements)

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“…Several mechanisms of chemoresistance have been described in solid cancers, that can be cell-intrinsic (23) or acquired during the course of the treatment (24). In NSCLC, it has been shown that galectin 1 expressed by tumor cells induces chemoresistance through upregulation of p38MAPK and ERK (25), and that nicotine induces STAT3 phosphorylation, leading to the serine/threonine kinase IKBKE oncogene activation, which leads to chemoresistance (26). However, to date, no biomarker is currently used to predict response to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

TLR7 Promotes Tumor Progression, Chemotherapy Resistance, and Poor Clinical Outcomes in Non–Small Cell Lung Cancer

et al. 2014

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Toll-like receptors (TLR) recognize pathogen molecules and danger-associated signals that stimulate inflammatory processes. TLRs have been studied mainly in antigen-presenting cells, where they exert important immune regulatory functions, but they are also expressed by epithelial tumor cells, where they have been implicated in tumor progression. In this study, we demonstrate that the injection of TLR7 agonist in NOD/SCID mice, in C57BL/6 wild-type, and TLR7-deficient mice grafted with lung adenocarcinoma tumor cells leads to increased tumor progression and chemotherapeutic resistance. In patients with non-small cell lung cancer, expression analyses revealed that high TLR7 expression was strongly associated with resistance to neoadjuvant chemotherapy and poor clinical outcomes. Our findings delineate a crucial role for TLR7 in lung cancer physiopathology. Cancer Res; 74(18); 5008-18. Ó2014 AACR.

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Section: Introductionmentioning

confidence: 99%

TLR7 Promotes Tumor Progression, Chemotherapy Resistance, and Poor Clinical Outcomes in Non–Small Cell Lung Cancer

et al. 2014

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“…This is seen in TGTs that are particularly sensitive to CDDP because they are one of the few cancers in which p53 is rarely inactivated (6). Activation of p38 MAPK, a kinase involved in apoptosis induction, is also altered in CDDP-resistant lung cells (7,8). Prosurvival signals, such as PI3K-AKT or extracellular signal-regulated kinases (ERK), are overstimulated in some CDDPresistant cells, such as lung or ovarian cell lines (3).…”

Section: Introductionmentioning

confidence: 99%

The PDGFRβ–AKT Pathway Contributes to CDDP-Acquired Resistance in Testicular Germ Cell Tumors

Juliachs

Muñoz

Moutinho

et al. 2014

Clinical Cancer Research

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Purpose: We examined whether PI3K-AKT or extracellular signal-regulated kinase (ERK) signaling pathways could play a role in the development of cisplatin (CDDP) resistance in testicular germ cell tumor (TGT) cells.Experimental Design: We compared AKT and ERK activation levels in CDDP-sensitive testicular tumor cells and in their corresponding CDDP-resistant-derived cells. We also analyzed these pathways in orthotopic testicular tumors and human patient samples.Results: Our results indicated that there was overactivation of AKT in CDDP-resistant cells compared with sensitive cells, but no effect on activated ERK levels. We observed an increase in mRNA and protein levels for platelet-derived growth factor (PDGF) receptor b and PDGF-B ligand. These were responsible for AKT overactivation in CDDP-resistant cells. When PDGFRb levels were decreased by short hairpin RNA (shRNA) treatment or its activation was blocked by pazopanib, CDDP-resistant cells behaved like sensitive cells. Moreover, CDDP-resistant cells were more sensitive to incubation with PDGFRb inhibitors such as pazopanib or sunitinib than sensitive cells, a finding consistent with these cells being dependent on this signaling pathway. We also found overexpression of PDGFRb and pAKT in CDDP-resistant choriocarcinoma orthotopic tumor versus their CDDP-sensitive counterparts. Finally, we found high PDGFRb levels in human testicular tumors, and overexpression in CDDP-resistant testicular choriocarcinomas compared with the CDDP-sensitive and nontreated tumors.Conclusions: The PDGFRb-AKT pathway plays a critical role in the development of CDDP resistance in testicular tumoral cells. Clin Cancer Res; 20(3); 658-67. Ó2013 AACR.

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“…14 Recent studies report that Gal-1 knockdown can sensitize melanoma and lung cancer cells to chemotherapy. 15,16 Previous studies have suggested that Gal-1 may serve as a potential marker for RCC. 17,18 However, the detailed molecular mechanisms connecting Gal-1 to RCC remain largely unknown.…”

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confidence: 99%

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Huang

Tang

Chung

et al. 2014

Journal of the American Society of Nephrology

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Galectin-1, a b-galactoside-binding lectin, is involved in many physiologic and pathologic processes, including cell adhesion, differentiation, angiogenesis, and tumor progression. However, the role of galectin-1 in kidney cancer remains elusive. This study evaluated the role of galectin-1 in the progression and clinical prognosis of renal cell carcinoma. We found significant overexpression of galectin-1 in both kidney cancer cell lines and metastatic tissue specimens from patients with renal cell carcinoma. Knockdown of galectin-1 gene expression in renal cancer cell lines reduced cell invasion, clonogenic ability, and epithelial-mesenchymal transition in vitro; reduced tumor outgrowth in vivo; and inhibited the angiogenesis-inducing activity of these cells in vitro and in vivo. Galectin-1 knockdown decreased CXCR4 expression levels in kidney cancer cells, and restoration of CXCR4 expression in galectin-1-silenced cells rescued cell motility and clonogenic ability. Additional studies suggested that galectin-1 induced CXCR4 expression through activation of nuclear factor-kB (NF-kB). Analysis of patient specimens confirmed the clinical significance and positive correlation between galectin-1 and CXCR4 expression levels and revealed concomitant overexpression of galectin-1 and CXCR4 associated adversely with overall and disease-free survival. Our findings suggest that galectin-1 promotes tumor progression through upregulation of CXCR4 via NF-kB. The coordinated upregulation of galectin-1 and CXCR4 may be a novel prognostic factor for survival in patients with renal cell carcinoma and the galectin-1-CXCR4 axis may serve as a therapeutic target in this disease. 25: 148625: -149525: , 201425: . doi: 10.1681 Renal cell carcinoma (RCC) accounts for approximately 4% of all adult malignancies. 1 More than one third of patients will present with locally advanced or metastatic disease at the time of diagnosis. 2 The 5-year survival rate of metastatic RCC is only 10% because of resistance to chemotherapy and radiation therapy. 3 Although cytokine therapy with IFN-a and IL-2 is the gold standard treatment, its overall efficacy rate is limited by its significant toxicity. 4 Recently, several molecular targeting drugs, including sunitinib and temsirolimus, have been approved for advanced RCC. 4 However, treatment response is not long-standing and overall survival remains poor. Thus, the identification of novel molecular targets in RCC is urgently needed for the development of effective therapies. J Am Soc Nephrol

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Galectin-1 Promotes Lung Cancer Progression and Chemoresistance by Upregulating p38 MAPK, ERK, and Cyclooxygenase-2

Cited by 133 publications

References 44 publications

TLR7 Promotes Tumor Progression, Chemotherapy Resistance, and Poor Clinical Outcomes in Non–Small Cell Lung Cancer

TLR7 Promotes Tumor Progression, Chemotherapy Resistance, and Poor Clinical Outcomes in Non–Small Cell Lung Cancer

The PDGFRβ–AKT Pathway Contributes to CDDP-Acquired Resistance in Testicular Germ Cell Tumors

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

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