XB130, a Novel Adaptor Protein, Promotes Thyroid Tumor Growth

Abstract

Adaptor proteins with multimodular structures can participate in the regulation of various cellular functions. We have cloned a novel adaptor protein, XB130, which binds the p85␣ subunit of phosphatidyl inositol 3-kinase and subsequently mediates signaling through RET/ PTC in TPC-1 thyroid cancer cells. In the present study, we sought to determine the role of XB130 in the tumorigenesis in vivo and in related molecular mechanisms. In WRO thyroid cancer cells, knockdown of XB130 using small interfering RNA inhibited G 1 -S phase progression, induced spontaneous apoptosis, and enhanced intrinsic and extrinsic apoptotic stimulus-induced cell death. Growth of tumors in nude mice formed from XB130 shRNA stably transfected WRO cells were significantly reduced, with decreased cell proliferation and increased apoptosis. Microarray analysis identified 246 genes significantly changed in XB130 shRNA transfected cells. Among them, 57 genes are related to cell proliferation or survival, including many transcription regulators. Ingenuity Pathway Analysis showed that the topranked disease related to XB130 is cancer, and the top molecular and cellular functions are cellular growth and proliferation and cell cycle. A human thyroid tissue microarray study identified expression of XB130 in normal thyroid tissue as well as in human thyroid carcinomas. These observations suggest that the expression of XB130 in these cancer cells may affect cell proliferation and survival by controlling the expression of multiple genes, especially transcription regulators.

XB130 expression in human osteosarcoma: a clinical and experimental study

“…Growth of tumors in nude mice formed from XB130 shRNA stably transfected WRO cells were significantly reduced, with decreased cell proliferation and increased apoptosis [12]. In the present study, we found that knockdown of XB130 inhibited invasion and mobility in OS cells in vitro, but the molecular contribution of XB130 in lung metastasis of OS cancer is still unknown.…”

“…XB130 has been detected in human esophageal squamous cell carcinoma (ESCC) [11], follicular and papillary thyroid carcinoma, as well as in human lung carcinoma cell lines [12]. In ESCC cells, expression of XB130 may affect cell cycle progression and impact prognosis of patients with ESCC [11].…”

“…In ESCC cells, expression of XB130 may affect cell cycle progression and impact prognosis of patients with ESCC [11]. In thyroid and lung cancer cells, XB130 has been implicated as a substrate and regulator of tyrosine kinase-mediated signaling and in controlling cell proliferation and apoptosis [12]. In the gastric cancer, reduced XB130 protein expression is a prognostic biomarker ego, CA) supplemented with 10% FCS, 2 mM glutamine, and 1% nonessential amino acids (complete medium).…”

XB130: A novel adaptor protein in cancer signal transduction

“…As previously mentioned, XB130 expression could be detected in various normal tissues of human including spleen, thyroid, kidney, lung, brain and pancreas (54). The expression of XB130 was detected in normal esophageal glands and in the cytoplasm of thyroid follicular cells in normal thyroid tissue, and no expression was identified in the normal epithelium (48,49,54). These findings indicate that XB130 may have an important role in normal glandular apparatus.…”

“…Shiozaki et al (48) found that XB130 was highly expressed in human thyroid cancers. The in vitro study by Lodyga et al (49) of the TPC1 cell line identified that downregulation of XB130 in the TPC1 cell line derived from papillary thyroid carcinoma led to proliferation reduction and anoikis promotion.…”