Regulation of the NRSF/REST gene by methylation and CREB affects the cellular phenotype of small-cell lung cancer

TSPYL2 is an essential component of the REST/NRSF transcriptional complex for TGFβ signaling activation

“…39 Loss of REST protein, or the expression of aberrant REST transcript variants encoding truncated REST proteins, has been reported in several types of human malignancies of epithelial origin, including breast, lung, and colon cancers. [6][7][8] In breast cancer, the loss of FL REST protein, in favor of a shorter carboxyterminal truncated form has been described in a small fraction of cases and is associated with disease recurrence and poor prognosis. 8 Accordingly, we provide evidence that both TSPYL2 and RESTare important for tumor suppression in epithelial cells, as knockdown of either gene or overexpression of TrkC was sufficient for the acquirement of the ability of anchorageindependent growth in HMECs.…”

“…5 Focal genomic deletions targeting the REST locus have been found in colon adenocarcinoma and REST protein expression is often lost in small cell lung carcinoma cells. 6,7 In breast cancer, the loss of full-length (FL) REST protein is associated with disease recurrence and poor prognosis.8 However, the underlying mechanism of how REST protects against transformation in epithelial tissues has remained largely elusive.We have previously implicated the testis-specific protein, Y-encoded-like (TSPY-L) family of genes in cancer by identifying TSPYL5 expression as a prognostic marker of poor clinical outcome in breast cancer.9 TSPYL5 can interfere with p53-dependent cell-cycle arrest and oncogene-induced senescence triggering p53 ubiquitination and protein degradation.9 Besides TSPYL5, the TSPYL family of genes includes several other members (four coding genes and one pseudogene) whose functions are still unknown. All five proteins (TSPYL1, TSPYL2, TSPYL4, TSPYL5, and TSPYL6) are characterized by a predicted nucleosome assembly protein (NAP) domain, although functional evidence of NAP activity has not been reported of any of the TSPYL family members.…”

“…5 Focal genomic deletions targeting the REST locus have been found in colon adenocarcinoma and REST protein expression is often lost in small cell lung carcinoma cells. 6,7 In breast cancer, the loss of full-length (FL) REST protein is associated with disease recurrence and poor prognosis. 8 However, the underlying mechanism of how REST protects against transformation in epithelial tissues has remained largely elusive.…”

A Prominent Couple

“…In small cell lung cancer cell lines, redued REST transcript levels resulted in increased expression of L1CAM and NCAM [103]. L1CAM has been identified as a neuronal cell adhesion molecule that plays an important role in the nervous system development by regulating neuronal migration and adhesion, and guidance of neurite outgrowth [104].…”

“…Several signaling mediators have been implicated in NED including neuropeptides (bombesin/gastrin-releasing peptide, calcitonin, serotonin, and vasoactive intestinal peptide) [97], cytokines (IL-6, IL-1β, IL-8) [98][99][100], ionizing irradiation [101], and stimuli elevating intra-cellular cAMP (such as forskolin) [102]. LNCaP cells cultured with cAMP or charcoal-stripped fetal bovine serum acquired a NE phenotype [103,104]. cAMP further induced G1 growth arrest in LNCaP cell [104] and synergized with IL-6, a prominent inducer of NED [105].…”