Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Sun, Hong; Shu, Wu; Tu, Zeng

doi:10.1038/sj.cr.7290075

Cited by 52 publications

(32 citation statements)

References 27 publications

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“…In patients with human epidermal growth factor receptor 2-negative breast cancer, the decreased expression of IGF1R was correlated with an improved response to chemotherapy (59). Blocking IGF1R signaling facilitates treating bladder cancer cells that are insensitive to chemotherapy (60). Similar phenomena have been reported for prostate and ovarian cancer when IGF1R signaling is blocked (61,62).…”

Section: Igf1r and Chemotherapy Resistancesupporting

confidence: 51%

Function of insulin‑like growth factor 1 receptor in cancer resistance to chemotherapy (Review)

et al. 2017

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Abstract. Drug resistance is a primary cause of chemotherapeutic failure; however, how this resistance develops is complex. A comprehensive understanding of chemotherapeutic resistance mechanisms may aid in identifying more effective drugs and improve the survival rates of patients with cancer. Insulin-like growth factor 1 receptor (IGF1R), a member of the insulin receptor family, has been extensively assessed for biological activity, and its putative contribution to tumor cell development and progression. Furthermore, researchers have attended to drugs that target IGF1R since IGF1R functions as a membrane receptor. However, how IGF1R participates in chemotherapeutic resistance remains unclear. Therefore, the present study described the IGF1R gene and its associated signaling pathways, and offered details of IGF1R-induced tumor chemoresistance associated with promoting cell proliferation, inhibition of apoptosis, regulation of ATP-binding cassette transporter proteins and interactions with the extracellular matrix. The present study offered additional explanations for tumor chemotherapy resistance and provided a theoretical basis of IGF1R and its downstream pathways for future possible chemotherapy treatment options.

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Section: Igf1r and Chemotherapy Resistancesupporting

confidence: 51%

Function of insulin‑like growth factor 1 receptor in cancer resistance to chemotherapy (Review)

et al. 2017

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“…IGF1R targeting has been linked with enhancement of chemosensitivity in several tumour cell types. In bladder cancer, IGF1R antisense oligonucletide transfection was shown to enhance sensitivity to mitomycin-C. 55 Scotlandi et al 56,57 demonstrated dramatic (410-fold) sensitization to doxorubicin in Ewing's sarcoma cells using IGF1R antisense, dominant negative receptor or monoclonal antibody. 58 It is possible that the greater magnitude of chemosensitization in this tumor may relate to the fact that, unlike prostate cancer, Ewing's sarcoma is inherently chemosensitive.…”

Section: Igf1r Gene Silencing Enhances Sensitivity To Dna-damaging Agmentioning

confidence: 99%

Silencing of the IGF1R gene enhances sensitivity to DNA-damaging agents in both PTEN wild-type and mutant human prostate cancer

et al. 2004

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The type 1 insulin-like growth factor receptor (IGF1R) is overexpressed in prostate cancer, and mediates proliferation, motility, and survival. Many prostate cancers harbor inactivating PTEN mutations, enhancing Akt phosphorylation. This activates the principal antiapoptotic pathway downstream of the IGF1R, calling into question the value of IGF1R targeting in this tumor. The aim of the current study was to assess the effect of IGF1R gene silencing in prostate cancer cells that lack functional PTEN protein. In human DU145, LNCaP and PC3 prostate cancer cells, transfection with IGF1R small interfering RNA induced significant enhancement of apoptosis and inhibition of survival, not only in PTEN wild-type DU145 but also in PTEN mutant LNCaP and PC3. This was attributed to attenuation of IGF signaling via Akt, ERKs and p38. In both DU145 and PC3, IGF1R knockdown led to enhancement of sensitivity to mitoxantrone, etoposide, nitrogen mustard and ionizing radiation. There was no sensitization to paclitaxel or 5-fluorouracil, which do not damage DNA, suggesting that chemosensitization results from impairment of the DNA damage response, in addition to removal of apoptosis protection. These results support the concept of IGF1R targeting in prostate cancer, and indicate that PTEN loss does not render tumor cells refractory to this strategy.

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“…These factors have been implicated in chronic inflammatory diseases, 55 prostate, 56 and bladder cancer. 57 Overexpression of IGF-I and underexpression of IGFBP 3 and 5 may lead to hyperplasia of the bladder smooth muscle. 58 Interestingly, IGF is decreased in the urine of IC patients 59 and an anti-proliferative factor purified from urothelial cells of IC patients has been shown to stimulate the production of IGF binding protein 3.…”

Section: Insulin-like Growth Factorsmentioning

confidence: 99%

Gene Expression Profiling of Mouse Bladder Inflammatory Responses to LPS, Substance P, and Antigen-Stimulation

Saban

Nguyen

Hammond

et al. 2002

The American Journal of Pathology

110

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Inflammatory bladder disorders such as interstitial cystitis (IC) deserve attention since a major problem of the disease is diagnosis. IC affects millions of women and isClinical and animal models of acute and chronic urinary bladder inflammation have provided several lines of evidence suggesting a central role of mast cells, sensory nerves, and neurokinin (NK)-1 receptors. Fundamental work regarding the participation of sensory nerves and mast cells in cystitis provides indirect evidence, such as increased numbers of mast cells in the detrusor and submucosa, and morphological evidence of mast cell activation and degranulation. [1][2][3][4] In addition, the extensive tissue remodeling seen in some clinical forms of bladder inflammation such as interstitial cystitis, 4 along with increased urinary levels of histamine and tryptase 5 suggest a role for mast cells. Because both mast cells 6 -8 and NK-1 receptors are increased in bladder biopsies of interstitial cystitis (IC) patients, 9,10 it is tempting to propose a role for sensory peptides-mast cell communication in the pathogenesis of this disorder.Experimentally, we have used classical morphometric analysis and microarray technology to determine the role of mast cells, NK-1 receptors, and bacterial toxins in animal models of cystitis. Time-course experiments indicated early and late genes involved in bladder inflammatory responses. 11 The availability of mice genetically deficient in neurokinin-1 receptor (NK-1R Ϫ/Ϫ ) allowed us to propose a mandatory role of SP receptors in cystitis. 12 We also determined genes that depend on the presence of tissue mast cells for their expression by comparing inflammatory responses in mast cell-deficient (Kit W /

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Blockage of IGF-1R signaling sensitizes urinary bladder cancer cells to mitomycin-mediated cytotoxicity

Cited by 52 publications

References 27 publications

Function of insulin‑like growth factor 1 receptor in cancer resistance to chemotherapy (Review)

Function of insulin‑like growth factor 1 receptor in cancer resistance to chemotherapy (Review)

Silencing of the IGF1R gene enhances sensitivity to DNA-damaging agents in both PTEN wild-type and mutant human prostate cancer

Gene Expression Profiling of Mouse Bladder Inflammatory Responses to LPS, Substance P, and Antigen-Stimulation

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