BEX2 is poor prognostic factor and required for cancer stemness in gastric cancer

Akihiro Yasumoto; Haruna Fujimori; Mai Mochizuki; Rie Shibuya-Takahashi; Mao Nakamura-Shima; Norihisa Shindo; Kazunori Yamaguchi; Daisuke Fukushi; Yuta Wakui; Takahiro Sugai; Wataru Iwai; Makoto Abue; Ikuro Sato; Kennichi Satoh; Yu Katayose; Jun Yasuda; Chikashi Shibata; Keiichi Tamai

doi:10.1016/j.bbrc.2023.03.025

BEX2 is poor prognostic factor and required for cancer stemness in gastric cancer

Biochem Biophys Res Commun. 2023 May 7:655:59-67. doi: 10.1016/j.bbrc.2023.03.025. Epub 2023 Mar 11.

Authors

Akihiro Yasumoto¹, Haruna Fujimori², Mai Mochizuki², Rie Shibuya-Takahashi², Mao Nakamura-Shima², Norihisa Shindo³, Kazunori Yamaguchi³, Daisuke Fukushi⁴, Yuta Wakui⁵, Takahiro Sugai⁵, Wataru Iwai⁵, Makoto Abue⁵, Ikuro Sato⁶, Kennichi Satoh⁴, Yu Katayose⁷, Jun Yasuda³, Chikashi Shibata⁸, Keiichi Tamai⁹

Affiliations

¹ Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1, Medeshima-Shiote, Natori, Miyagi, Japan; Division of Gastoroenterologic Surgery, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyaginoku, Sendai, Miyagi, 983-8536, Japan.
² Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1, Medeshima-Shiote, Natori, Miyagi, Japan.
³ Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, 47-1, Medeshima-Shiote, Natori, Miyagi, Japan.
⁴ Division of Gastroenterology, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyaginoku, Sendai, Miyagi, 983-8536, Japan.
⁵ Department of Gastroenterology, Miyagi Cancer Center, 47-1, Medeshima-Shiote, Natori, Miyagi, Japan.
⁶ Department of Pathology, Miyagi Cancer Center, 47-1, Medeshima-Shiote, Natori, Miyagi, Japan.
⁷ Division of Hepato-biliary-pancreatic Surgery, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyaginoku, Sendai, Miyagi, 983-8536, Japan.
⁸ Division of Gastoroenterologic Surgery, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyaginoku, Sendai, Miyagi, 983-8536, Japan.
⁹ Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1, Medeshima-Shiote, Natori, Miyagi, Japan. Electronic address: tamaikeiichi@med.tohoku.ac.jp.

PMID: 36933308
DOI: 10.1016/j.bbrc.2023.03.025

Abstract

Gastric cancer is the fifth most common malignancy worldwide. However, targeted therapy for advanced gastric cancer is still limited. Here, we report BEX2 (Brain expressed X-linked 2) as a poor prognostic factor in two gastric cancer cohorts. BEX2 expression was increased in spheroid cells, and its knockdown decreased aldefluor activity and cisplatin resistance. BEX2 was found to upregulate CHRNB2 (Cholinergic Receptor Nicotinic Beta 2 Subunit) expression, a cancer stemness-related gene, in a transcriptional manner, and the knockdown of which also decreases aldefluor activity. Collectively, these data are suggestive of the role of BEX2 in the malignant process of gastric cancer, and as a promising therapeutic target.

Keywords: BEX2; CHRNB2; Gastric cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Humans
Nerve Tissue Proteins / metabolism
Oncogenes
Prognosis
Stomach Neoplasms* / diagnosis
Stomach Neoplasms* / genetics

Substances

BEX2 protein, human
Nerve Tissue Proteins