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World J Stem Cells. Jan 26, 2022; 14(1): 41-53
Published online Jan 26, 2022. doi: 10.4252/wjsc.v14.i1.41
Multiple roles of mothers against decapentaplegic homolog 4 in tumorigenesis, stem cells, drug resistance, and cancer therapy
Chuan-Jing Dai, Yu-Ting Cao, Fang Huang, Yi-Gang Wang
Chuan-Jing Dai, Yu-Ting Cao, Yi-Gang Wang, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
Fang Huang, Department of Pathology, Zhejiang Provincial People’s Hospital of Hangzhou Medical University, Hangzhou 310014, Zhejiang Province, China
Author contributions: Dai CJ wrote the paper; Cao YT and Huang F wrote the partial manuscript, and contributed equally to this work; Wang YG designed the layout of the review and edited the manuscript.
Supported by the National Natural Science Foundation of China, No. 8180306; the Natural Science Foundation of Zhejiang Province, No. LY18C070002; and the 521 Talent Project of Zhejiang Sci-Tech University, No. 2021437620 and No. 2019337459.
Conflict-of-interest statement: The authors do not have any possible conflicts of interest to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Yi-Gang Wang, PhD, Professor, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, No. 2 Street of Xiasha District, Hangzhou 310018, Zhejiang Province, China.
Received: March 16, 2021
Peer-review started: March 16, 2021
First decision: May 5, 2021
Revised: May 13, 2021
Accepted: December 21, 2021
Article in press: December 21, 2021
Published online: January 26, 2022
Core Tip

Core Tip: Mothers against decapentaplegic homolog 4 (Smad4) is regarded as a tumor suppressor. Recent studies have shown that Smad4 plays a tumor-promoting role in specific types of cancer, rather than a tumor-suppressing role. Smad4 also correlates with the stem cells fate and drug resistance of cancer cells. Elucidating the specific role of Smad4 is of positive guiding significance for understanding the mechanism of tumorigenesis and cancer treatment. In this review, we focus on the multiple roles of Smad4 in tumorigenesis, stem cells, and drug resistance, and provide novel insights into the prospect of Smad4 in combination therapy.