The purpose of this project is to investigate molecular mechanisms involved in the response of cells to hyperthermia. We will concentrate on determining the effect of clinically relevant hyperthermia doses an the functions of membrane enzyme systems involved in transmembrane signaling. Our preliminary data indicates that hyperthermia produces rapid and profound stimulation of the 3 major such systems. These are the adenylate cyclase, phospholipase C and phospholipase A2 systems. As these signaling systems are intimately involved in regulating all of the major functions of cells (proliferation, differentiation, metabolism, etc.) Their stimulation by hyperthermia may be highly significant. We will investigate the hypothesis that activation of transmembrane signal pathways generates cascade responses at the plasma membrane. These cascade responses may then be involved in mediating thermal cell killing, inducing thermotolerance and modulating tumor blood flow and cellular radiosensitivity. We will additionally examine the hypothesis that a common component of all signal transduction systems, the guanine nucleotide binding protein, constitutes a universal target for hyperthermia.
We aim to test the possibility that these proteins may serve as transducers of the physical effects of hyperthermia just as they transduce the chemical messages of hormones and other signalling agonists.
| Murshid, Ayesha; Prince, Thomas L; Lang, Ben et al. (2018) Role of Heat Shock Factors in Stress-Induced Transcription. Methods Mol Biol 1709:23-34 |
| Murshid, Ayesha; Theriault, Jimmy; Gong, Jianlin et al. (2018) Molecular Chaperone Receptors. Methods Mol Biol 1709:331-344 |
| Eguchi, Takanori; Calderwood, Stuart K; Takigawa, Masaharu et al. (2017) Intracellular MMP3 Promotes HSP Gene Expression in Collaboration With Chromobox Proteins. J Cell Biochem 118:43-51 |
| Calderwood, Stuart K; Gong, Jianlin (2016) Heat Shock Proteins Promote Cancer: It's a Protection Racket. Trends Biochem Sci 41:311-323 |
| Calderwood, Stuart K; Neckers, Len (2016) Hsp90 in Cancer: Transcriptional Roles in the Nucleus. Adv Cancer Res 129:89-106 |
| Gong, J; Weng, D; Eguchi, T et al. (2015) Targeting the hsp70 gene delays mammary tumor initiation and inhibits tumor cell metastasis. Oncogene 34:5460-71 |
| Bunch, Heeyoun; Lawney, Brian P; Lin, Yu-Fen et al. (2015) Transcriptional elongation requires DNA break-induced signalling. Nat Commun 6:10191 |
| Murshid, Ayesha; Gong, Jianlin; Prince, Thomas et al. (2015) Scavenger receptor SREC-I mediated entry of TLR4 into lipid microdomains and triggered inflammatory cytokine release in RAW 264.7 cells upon LPS activation. PLoS One 10:e0122529 |
| Murshid, Ayesha; Gong, Jianlin; Ahmad, Ridwan et al. (2015) Scavenger receptor SREC-I promotes double stranded RNA-mediated TLR3 activation in human monocytes. Immunobiology 220:823-32 |
| Eguchi, Taka; Prince, Thomas; Wegiel, Barbara et al. (2015) Role and Regulation of Myeloid Zinc Finger Protein 1 in Cancer. J Cell Biochem 116:2146-54 |
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