Cyclin D1 is well known as a DNA repair gene and might sensitize human cancers to radiation by limiting DNA repair. In breast cancer, overexpression of cyclin D induces www.selleckchem.com/products/INCB18424.html radiation resistance by inhibiting apoptosiss. In our analysis, CCND1 was downregulated in radiosensitive cell lines, consistent with this explanation. Annexins including ANXA2 and ANXA5 are family of Ca2 regulated membrane binding proteins that interact with the cellular membrane. ANXA5, in particular, is related to induction of apoptosis and is used as an apoptosis marker. ACTN1, WAS, HCLS1, RAB13, and PFN2 are involved with cellular junctions and the actin cytoskeleton, and PTPRC is known for interacting with cell adhesion molecules. Cel lular adhesion mediated radioresistance is proposed to generate anti apoptotic signals when integrin mediated adhesion interacts with the extracellular matrix.

Integrins are adhesion molecules localized in the plasma membrane, and are heterodimeric glycoprotein receptors of and B subunits. They directly bind to the ECM and contribute to proliferation, survival, and invasion in cancer. In radiation biology, several studies report integrins as prognostic or therapeutic markers in several cancer types including breast, head and neck, prostate, lung, and colon cancer. In addition to integrin B1, which was included in our identified 179 genes and the most studied relative to radiosensitivity, our study identified integrin B5 as a radiosensitive gene. vB5 receptors are con sidered to be potential therapeutic targets because of their anti angiogenic and anti metastatic effects, and cilengiti dem, which is known as vB5 antagonist, has been studied in anti cancer therapy.

Likewise, ITGB5 could be a potential biomarker as a prognostic marker or radiosensi tizer in radiotherapy. Using systems biology, we showed that major cancer related signaling pathways were enriched related to radiosensitivity and that the integrin signaling pathway interacts with other pathways, including MAPK, Wnt, and PI3K signaling, as shown in Figure 3B. These findings suggest that integrin signaling with identified adhesion molecules could be central in radiosensitivity and one of the common radiosensitivity mechanisms, regardless of cell type. Our work could be the basis for future biological validation targeting integrin signaling pathways in radiosensitization.

Although we identified a common radiosensitivity sig nature Drug_discovery regardless of cell type, radiosensitive cells included cells of lymphoid origin and could have introduced bias in analysis. To exclude the effect of lymphoid origin, we adjusted correlation coefficients and p values between radiosensitive cells and radioresistant cells using mean centering and a standardization method. We observed that correlation coefficients of the 31 radiosen sitivity signature genes were similar before and after ad justment for the four microarrays.