HUNK inhibits epithelial-mesenchymal transition of CRC via direct phosphorylation of GEF-H1 and activating RhoA/LIMK-1/CFL-1

Han, Xiaoqi; Jiang, Siyuan; Gu, Yinmin; Ding, Lihua; Zhao, Enyue; Cao, Dejun; Wang, Xiaodong; Wen, Ya; Pan, Yongbo; Yan, Xin; Duan, Liqiang; Sun, Min; Zhou, Tao; Liu, Yajuan; Hu, Hongbo; Ye, Qinong; Gao, Shan

doi:10.1038/s41419-023-05849-2

Cited by 6 publications

(2 citation statements)

References 40 publications

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“…Accumulating evidence has shown that EMT process is the key regulatory of metastasis of various kinds of tumors including BLCA 33–35 . Despite the significant clinical challenge posed by EMT in BLCA treatment, the identification of key regulators through this process offers potential for the development of promising prognosis predictor and therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

POLR3G promotes EMT via PI3K/AKT signaling pathway in bladder cancer

Chen,

Ma,

Yang

et al. 2023

The FASEB Journal

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RNA Polymerase III Subunit G (POLR3G) promotes tumorigenesis, metastasis, cancer stemness, and chemoresistance of breast cancer and lung cancer; however, its biological function in bladder cancer (BLCA) remains unclear. Through bioinformatic analyses, we found that POLR3G expression was significantly elevated in BLCA tumor tissues and was associated with decreased survival. Multivariate Cox analysis indicated that POLR3G could serve as an independent prognostic risk factor. Our functional investigations revealed that POLR3G deficiency resulted in reduced migration and invasion of BLCA cells both in vitro and in vivo. Additionally, the expressions of EMT‐related mesenchymal markers were also downregulated in POLR3G knockdown cells. Mechanistically, we showed that POLR3G could activate the PI3K/AKT signaling pathway. Inhibition of this pathway with LY294002 reduced the enhanced migration and invasion of BLCA cells induced by POLR3G overexpression, whereas the activation of this pathway using 740Y‐P restored the abilities that were inhibited by POLR3G knockdown. Taken together, our findings suggested that POLR3G is a prognostic predictor for BLCA and promotes EMT of BLCA through activation of the PI3K/AKT signaling pathway.

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Section: Discussionmentioning

confidence: 99%

POLR3G promotes EMT via PI3K/AKT signaling pathway in bladder cancer

Chen,

Ma,

Yang

et al. 2023

The FASEB Journal

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“…Additionally, HUNK phosphorylates GEF-H1 at serine 645, which consequently activates RhoA and further phosphorylates LIMK-1/CFL-1. By this means, the stability of F-actin is improved, and CRC metastasis is inhibited [28] (Figure 2).…”

Section: Phosphorylation Regulates Cytoskeleton Rearrangementmentioning

confidence: 98%

Role of Post-Translational Modifications in Colorectal Cancer Metastasis

Peng,

Liu,

Hai

et al. 2024

Cancers

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Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract. CRC metastasis is a multi-step process with various factors involved, including genetic and epigenetic regulations, which turn out to be a serious threat to CRC patients. Post-translational modifications (PTMs) of proteins involve the addition of chemical groups, sugars, or proteins to specific residues, which fine-tunes a protein’s stability, localization, or interactions to orchestrate complicated biological processes. An increasing number of recent studies suggest that dysregulation of PTMs, such as phosphorylation, ubiquitination, and glycosylation, play pivotal roles in the CRC metastasis cascade. Here, we summarized recent advances in the role of post-translational modifications in diverse aspects of CRC metastasis and its detailed molecular mechanisms. Moreover, advances in drugs targeting PTMs and their cooperation with other anti-cancer drugs, which might provide novel targets for CRC treatment and improve therapeutic efficacy, were also discussed.

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