HECW2 promotes the progression and chemoresistance of colorectal cancer via AKT/mTOR signaling activation by mediating the ubiquitin-proteasome degradation of lamin B1

Fang Li; Li Wang; Yujue Wang; Hui Shen; Qianrui Kou; Changjun Shen; Xiangrong Xu; Yunqing Zhang; Jing Zhang

doi:10.7150/jca.87545

HECW2 promotes the progression and chemoresistance of colorectal cancer via AKT/mTOR signaling activation by mediating the ubiquitin-proteasome degradation of lamin B1

J Cancer. 2023 Sep 4;14(15):2820-2832. doi: 10.7150/jca.87545. eCollection 2023.

Authors

Fang Li¹, Li Wang¹, Yujue Wang¹, Hui Shen¹, Qianrui Kou¹, Changjun Shen², Xiangrong Xu¹, Yunqing Zhang³, Jing Zhang¹

Affiliations

¹ Medical School of Yan'an University, Yan'an 716000, China.
² Yan'an People's Hospital, Yan'an 716000, China.
³ Yan'an University Affiliated Hospital, Yan'an 716000, China.

Abstract

Colorectal cancer (CRC) is among the most common malignancies worldwide. Although a recent study has shown that E3 ubiquitin ligases play a major role in regulating the occurrence and development of CRC, there are few reports on the role of the E3 ubiquitin ligase HECW2(HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) in CRC progression and chemoresistance. We found that HECW2 is highly expressed in CRC tissues. HECW2 knockdown inhibits CRC progression and chemoresistance, whereas HECW2 overexpression has the opposite effect. Mechanistically, HECW2 activates the AKT/mTOR signaling pathway by mediating the ubiquitin-proteasome degradation of lamin B1, thereby promoting CRC progression and chemoresistance. Our findings suggest that HECW2 may be a promising novel therapeutic target for CRC treatment.

Keywords: AKT/mTOR signaling pathway; HECW2; chemoresistance; colorectal cancer; lamin B1; progression.