Nicotine enhances the malignant potential of human pancreatic cancer cells via activation of atypical protein kinase C

Takehiko Hanaki, Yosuke Horikoshi, Kazuhiro Nakaso, Masato Nakasone, Yoshinori Kitagawa, Masataka Amisaki, Yosuke Arai, Naruo Tokuyasu, Teruhisa Sakamoto, Soichiro Honjo, Hiroaki Saito, Masahide Ikeguchi, Kazunari Yamashita, Shigeo Ohno, Tatsuya Matsura

研究成果: Article査読

17 被引用数 (Scopus)

抄録

Background Pancreatic cancer (PC) is the most lethal malignancy among solid tumors, and the most common risk factor for its development is cigarette smoking. Atypical protein kinase C (aPKC) isozymes function in cell polarity, proliferation, and survival, and have also been implicated in carcinogenesis. However, the involvement of aPKC in PC progression and the effect of nicotine, a major component of cigarette smoke, on the biological activities of aPKC remain to be fully elucidated. Methods We investigated the effects of nicotine on the proliferation, migration and invasion of the human PC cell lines Panc1 and BxPC3. We analyzed aPKC localization and activity by immunohistochemistry and in vitro kinase assays, respectively, to assess their involvement in the regulation of PC progression. Moreover, we examined the effect of nicotine on implanted peritoneal tumors of PC cells in mice. Results Nicotine enhanced cell proliferation, migration and invasion in Panc1 and BxPC3 cells. In nicotine-treated PC cells, the aPKC was significantly activated. We also found that nicotine induced phosphatidylinositol 3-kinase (PI3K) signal activation, and a specific inhibitor of the nicotine acetylcholine receptor (nAChR) as well as knockdown of nAChR prevented nicotine-mediated Akt phosphorylation and aPKC activation. In a peritoneal dissemination model of PC, nicotine-treated mice had larger tumors and increased numbers of nodules. Immunohistochemistry showed enhanced expression levels of aPKC and phosphorylated Akt in nodules from nicotine-treated mice. Conclusions and general significance Nicotine induces aberrant activation of aPKC via nAChR/PI3K signaling in PC cells, resulting in enhancement of cellular proliferation, migration and invasion.

本文言語English
ページ(範囲)2404-2415
ページ数12
ジャーナルBiochimica et Biophysica Acta - General Subjects
1860
11
DOI
出版ステータスPublished - 2016 11月 1
外部発表はい

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学

フィンガープリント

「Nicotine enhances the malignant potential of human pancreatic cancer cells via activation of atypical protein kinase C」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル