Proline-rich 11 (PRR11) promotes the progression of cutaneous squamous cell carcinoma by activating the EGFR signaling pathway
Proline-rich 11 (PRR11) promotes the progression of cutaneous squamous cell carcinoma by activating the EGFR signaling pathway
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DOI：
10.1002/mc.23510
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发表时间：
2023-02-02
影响因子：
4.6
通讯作者：
Zheng，Yan
中科院分区：
文献类型：
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作者：
Wang，Shengbang;Zhang，Xiu;Zheng，Yan
皮肤鳞状细胞癌(CSCC)是最常见的皮肤恶性肿瘤之一，其发病率在全球范围内呈上升趋势。富含脯氨酸的11(PRR11)已被报道参与多种肿瘤的发生发展。然而，PRR11在CSCC中的作用仍不清楚。在本研究中，我们观察到PRR11在CSCC组织和细胞系中表达上调。体外培养的A431和SCL-1细胞系通过诱导细胞周期停滞于G1/S期，抑制细胞增殖，促进细胞凋亡，减少细胞迁移和侵袭。反之，PRR11过表达促进细胞增殖，减少细胞凋亡，促进细胞迁移和侵袭。在小鼠异种移植模型中，PRR11基因敲除也抑制了CSCC肿瘤的生长。通过RNA测序的机制研究表明，891个基因是PRR11基因敲除细胞和对照细胞之间差异表达的基因。不同基因的富集度分析表明，表皮生长因子受体(EGFR)信号通路是最高富集度的途径。我们进一步验证了PRR11诱导了EGFR途径的活性，从而促进了CSCC的进展。这些数据表明，PRR11可能成为CSCC的一个新的治疗靶点。
Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin malignancies, and its incidence rate is increasing worldwide. Proline‐rich 11 (PRR11) has been reported to be involved in the occurrence and development of various tumors. However, the role of PRR11 in cSCC remains unknown. In the present study, we observed upregulated expression of PRR11 in cSCC tissues and cell lines. Knockdown of PRR11 in the cSCC cell lines A431 and SCL‐1 inhibited cell proliferation by inducing cell cycle arrest during the G1/S phase transition, promoted cell apoptosis, and reduced cell migration and invasion in vitro. Conversely, overexpression of PRR11 promoted cell proliferation, decreased cell apoptosis, and enhanced cell migration and invasion. PRR11 knockdown also inhibited cSCC tumor growth in a mouse xenograft model. Mechanistic investigations by RNA sequencing revealed that 891 genes were differentially expressed genes between cells with PRR11 knockdown and control cells. Enrichment analysis of different genes showed that the epidermal growth factor receptor (EGFR) signaling pathway was the top enriched pathway. We further validated that PRR11 induced EGFR pathway activity, which contributed to cSCC progression. These data suggest that PRR11 may serve as a novel therapeutic target in cSCC.