PBK promotes aggressive phenotypes of cervical cancer through ERK/c‐Myc signaling pathway,Journal of Cellular Physiology

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PBK promotes aggressive phenotypes of cervical cancer through ERK/c‐Myc signaling pathway
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-11-13 , DOI: 10.1002/jcp.30134
Hanlin Ma _{1,

2} , Fang Han ₃ , Xiaohui Yan ₄ , Gonghua Qi ₁ , Yingwei Li _{1,

5} , Rongrong Li _{1,

2} , Shi Yan _{1,

2} , Cunzhong Yuan _{1,

2} , Kun Song _{1,

2} , Beihua Kong _{1,

2}

Affiliation

Cervical cancer is the fourth most frequent cancer in women worldwide. PDZ‐binding kinase (PBK) is proven to promote the malignant behaviors of various carcinomas. However, its functional roles and oncogenic mechanisms in cervical cancer are poorly understood. In this study, we reported that PBK was highly expressed in cervical cancer tissues. PBK promoted the proliferation, metastasis, and cisplatin resistance of cervical cancer cells. OTS514, a specific PBK inhibitor, could significantly suppress proliferation and metastasis of cervical cancer cells in vitro and in a xenograft model. Besides, OTS514 could enhance cisplatin‐based chemosensitivity in cervical cancer cells. Mechanistically, PBK promoted the expression and stabilization of c‐Myc through phosphorylating ERK1/2. OTS514 suppressed the phosphorylation of ERK1/2 and the transcriptional activity of c‐Myc. Furthermore, inhibition of the ERK signal pathway by U0126 reversed the increased proliferation and metastasis induced by overexpression of PBK. Exogenous expression of c‐Myc counteracted the decreased proliferation and metastasis evoked by knockdown of PBK. In conclusion, PBK promoted the malignant progression of cervical cancer through ERK/c‐Myc signal pathway. PBK might be a promising molecular target for cervical cancer treatment.

中文翻译：

PBK通过ERK/c-Myc信号通路促进宫颈癌侵袭表型

宫颈癌是全球女性第四常见的癌症。 PDZ结合激酶（PBK）被证明可促进多种癌症的恶性行为。然而，其在宫颈癌中的功能作用和致癌机制尚不清楚。在这项研究中，我们报道了PBK在宫颈癌组织中高表达。 PBK促进宫颈癌细胞的增殖、转移和顺铂耐药。 OTS514是一种特异性PBK抑制剂，可在体外和异种移植模型中显着抑制宫颈癌细胞的增殖和转移。此外，OTS514 可以增强宫颈癌细胞对顺铂的化疗敏感性。从机制上讲，PBK 通过磷酸化 ERK1/2 促进 c-Myc 的表达和稳定。 OTS514 抑制 ERK1/2 的磷酸化和 c-Myc 的转录活性。此外，U0126 对 ERK 信号通路的抑制逆转了 PBK 过表达诱导的增殖和转移增加。 c-Myc 的外源表达抵消了 PBK 敲低引起的增殖和转移减少。总之，PBK通过ERK/c-Myc信号通路促进宫颈癌的恶性进展。 PBK 可能是宫颈癌治疗的一个有前景的分子靶点。

更新日期：2020-11-13

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