基底细胞癌
中文名称
通路描述
皮肤癌是最常见的癌症，基底细胞癌（BCC）占所有皮肤癌的90%。绝大多数BCC病例是散发性的，但有一种罕见的家族性综合征基底细胞痣综合征（BCNS，或戈林综合征）会 predispose 到BCC的发生。此外，流行病学和遗传证据表明紫外线暴露是主要风险因素。基底细胞癌的发展与 Sonic hedgehog 信号通路的持续激活有关。SMOH、PTCH1 和 SHH 基因突变在BCC中导致靶基因的持续激活。在细胞水平上，Sonic hedgehog 信号通路促进细胞增殖。TP53 突变在散发性BCC中也以高频率（>50%）出现。
英文描述
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells) A conjunction of signaling from the T cell receptor, Interferon gamma (IFNG), and Interleukin-12 (IL12) induces the differentiation of T helper 1 cells (Th1) by activating the master regulator TBX21 (T-bet). Expression of TBX21 (T-bet) occurs in two phases. The first phase is dependent on IFNG acting via STAT1 and the T cell receptor acting via calcium, calcineurin, and NFATC1 (inferred from mouse homologs in Zhong et al. 2025). During the first phase, TBX21 activates expression of IL21RB2, a subunit of the receptor for IL12 (inferred from mouse homologs in Mullen et al. 2001, Afkarian et al. 2002, Schulz et al. 2009, Zhu et al. 2012). The second phase is dependent on IL12 acting via IL21RB2 and STAT4 (Inferred from mouse cells in Schulz et al. 2009, Wei et al. 2010, Zhu et al. 2012, Fang et al. 2022).
TBX21 with RUNX3 then enhances expression of IFNG (inferred from mouse homologs in Szabo et al. 2000, Mullen et al. 2001, Hatton et al. 2006, Djuretic et al. 2007, Jenner et al. 2009, Zhu et al. 2012), thereby creating a positive feedback loop that maintains TBX21 expression. TBX21 also binds the transcription factor RUNX1 and prevents RUNX1 from activating expression of RORC, an activator of Th17 differentiation (inferred from mouse homologs in Lazarevic et al. 2011). TBX21 also represses expression of IL4, an activator of Th2 differentiation (Jenner et al. 2009, and inferred from mouse homologs in Zhu et al. 2012). Thus, TBX21 restricts naive CD4+ T cells to the Th1 fate.
TBX21 then directly activates expression of Th1 regulators and cell markers, including C-X-C chemokine receptor type 3 (CXCR3) (inferred from mouse homologs in Szabo et al. 2000, Lord et al. 2005, Zhu et al. 2012, Gökmen et al. 2013), Tumor necrosis factor (TNF, TNFA) (Jenner et al. 2009, and inferred from mouse homologs in Zhu et al. 2012), C-C motif chemokine 3 (CCL3) (Jenner et al. 2009, and inferred from mouse homologs in supplement-02 of Zhu et al. 2012). TBX21 also upregulates expression of Proteinâtyrosine sulfotransferase 2 (TPST2) (inferred from mouse homologs in Lord et al. 2005), which is linked to the ability of Th1 cells to migrate and access inflamed skin (Pritchard et al. 2019).
TBX21 with RUNX3 then enhances expression of IFNG (inferred from mouse homologs in Szabo et al. 2000, Mullen et al. 2001, Hatton et al. 2006, Djuretic et al. 2007, Jenner et al. 2009, Zhu et al. 2012), thereby creating a positive feedback loop that maintains TBX21 expression. TBX21 also binds the transcription factor RUNX1 and prevents RUNX1 from activating expression of RORC, an activator of Th17 differentiation (inferred from mouse homologs in Lazarevic et al. 2011). TBX21 also represses expression of IL4, an activator of Th2 differentiation (Jenner et al. 2009, and inferred from mouse homologs in Zhu et al. 2012). Thus, TBX21 restricts naive CD4+ T cells to the Th1 fate.
TBX21 then directly activates expression of Th1 regulators and cell markers, including C-X-C chemokine receptor type 3 (CXCR3) (inferred from mouse homologs in Szabo et al. 2000, Lord et al. 2005, Zhu et al. 2012, Gökmen et al. 2013), Tumor necrosis factor (TNF, TNFA) (Jenner et al. 2009, and inferred from mouse homologs in Zhu et al. 2012), C-C motif chemokine 3 (CCL3) (Jenner et al. 2009, and inferred from mouse homologs in supplement-02 of Zhu et al. 2012). TBX21 also upregulates expression of Proteinâtyrosine sulfotransferase 2 (TPST2) (inferred from mouse homologs in Lord et al. 2005), which is linked to the ability of Th1 cells to migrate and access inflamed skin (Pritchard et al. 2019).
所含基因
11 个基因