Activin A promotes cell proliferation, invasion and migration and predicts poor prognosis in patients with colorectal cancer

Daitoku,Nobuya; Miyamoto,Yuji; Hiyoshi,Yukiharu; Tokunaga,Ryuma; Sakamoto,Yuki; Sawayama,Hiroshi; Ishimoto,Takatsugu; Baba,Yoshifumi; Yoshida,Naoya; Baba,Hideo

doi:10.3892/or.2022.8318

Activin A promotes cell proliferation, invasion and migration and predicts poor prognosis in patients with colorectal cancer

Authors:
- Nobuya Daitoku
- Yuji Miyamoto
- Yukiharu Hiyoshi
- Ryuma Tokunaga
- Yuki Sakamoto
- Hiroshi Sawayama
- Takatsugu Ishimoto
- Yoshifumi Baba
- Naoya Yoshida
- Hideo Baba
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Affiliations: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860‑8556, Japan
Published online on: April 20, 2022 https://doi.org/10.3892/or.2022.8318
Article Number: 107
Copyright: © Daitoku et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Activin A is a member of the transforming growth factor‑β superfamily of cytokines and displays various pathophysiological activities, including regulation of muscle catabolism and atrophy. Activin A expression is upregulated in several human cancer types and in certain pathologies, its expression is associated with poor prognosis. In the present study, activin A expression was assessed in colorectal cancer (CRC) tissue specimens from 157 patients with primary CRC and the relationship between activin A levels and clinicopathological characteristics, including skeletal muscle mass, and prognosis, was determined. Furthermore, the effects of knockdown of endogenous or exposure to exogenous activin A on the malignant behavior of human CRC cell lines were investigated in vitro. The results indicated that activin A mRNA was significantly upregulated in CRC tumor tissues compared with normal intestinal epithelium. High activin A expression was significantly associated with shorter cancer‑specific survival (P=0.047) and overall survival (P=0.014). According to a multivariate analysis, tumor activin A levels were an independent prognostic factor for overall survival (P=0.001). However, activin A mRNA levels were not associated with the skeletal muscle index. The in vitro experiments demonstrated that exposure to exogenous activin A increased the proliferation, invasion and migration of CRC cell lines, whereas knockdown of endogenous activin A had the opposite effects. In conclusion, activin A is an autocrine and paracrine regulator of CRC cell proliferation and high tumor expression of activin A is associated with poor prognosis in patients with CRC.

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