Protein phosphatase 6 promotes stemness of colorectal cancer cells

IF 4.5 2区医学 Q1 ONCOLOGY Cancer Science Pub Date : 2024-07-16 DOI:10.1111/cas.16271

Nobuyuki Fujiwara, Ryouichi Tsunedomi, Yuta Kimura, Masao Nakajima, Shinobu Tomochika, Shuhei Enjoji, Takashi Ohama, Koichi Sato, Hiroaki Nagano

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Abstract

Colorectal cancer (CRC) remains a significant global health concern, demanding a more profound comprehension of its molecular foundations for the development of improved therapeutic strategies. This study aimed to elucidate the role of protein phosphatase 6 (PP6), a member of the type 2A protein phosphatase family, in CRC. Protein phosphatase 6 functions as a heterotrimer with a catalytic subunit (PP6c), regulatory subunits (PP6Rs; PP6R1, PP6R2, and PP6R3), and scaffold subunits (ANKRD28, ANKRD44, and ANKRD52). Elevated PP6c expression has been identified in CRC tissues compared to normal mucosa, aligning with its potential involvement in CRC pathogenesis. PP6c knockdown resulted in decreased colony-forming ability and in vivo proliferation of various CRC cell lines. Transcriptome analysis revealed that PP6c knockdown resulted in altered expression of genes associated with cancer stemness. Notably, the PP6c-PP6R3 complex is a key player in regulating cancer stem cell (CSC) markers. Additionally, increased PP6c expression was observed in CSC-like cells induced by sphere formation, implicating the role of PP6c in CSC maintenance. This study highlights the role of PP6c in CRC and suggests that it is a potential therapeutic target disrupting a pathway critical for CRC progression and stem cell maintenance.

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蛋白磷酸酶 6 可促进结直肠癌细胞的干性。

结直肠癌（CRC）仍然是全球关注的重大健康问题，需要更深入地了解其分子基础，以制定更好的治疗策略。本研究旨在阐明 2A 型蛋白磷酸酶家族成员蛋白磷酸酶 6（PP6）在 CRC 中的作用。蛋白磷酸酶6是一种异源三聚体，具有催化亚基（PP6c）、调节亚基（PP6Rs；PP6R1、PP6R2和PP6R3）和支架亚基（ANKRD28、ANKRD44和ANKRD52）。与正常粘膜相比，PP6c 在 CRC 组织中的表达已被发现升高，这与它可能参与 CRC 发病有关。PP6c 基因敲除会导致各种 CRC 细胞系的集落形成能力和体内增殖能力下降。转录组分析表明，PP6c敲除导致与癌症干性相关的基因表达发生改变。值得注意的是，PP6c-PP6R3复合物是调控癌症干细胞（CSC）标志物的关键因素。此外，在球形成诱导的CSC样细胞中观察到PP6c表达增加，这表明PP6c在CSC维持中的作用。这项研究强调了PP6c在CRC中的作用，并表明PP6c是一个潜在的治疗靶点，可以破坏对CRC进展和干细胞维持至关重要的通路。

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来源期刊

Cancer Science 医学-肿瘤学

自引率

3.50%

发文量

406

审稿时长

2 months

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.

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