Traditional Chinese medicine as targeted treatment for epithelial‐mesenchymal transition‐induced cancer progression

Abstract

The epithelial‐mesenchymal transition (EMT) program, which loosens cell‐cell adhesion complexes, endows cells with enhanced migratory and invasive properties. Furthermore, this process facilitates both the development of drug resistance and immunosuppression by tumor cells, which preclude the successful treatment of cancer. Recent research has demonstrated that many signaling pathways are involved in EMT progression. In addition, cancer stem cells (CSCs), vasculogenic mimicry (VM) and the tumor‐related immune microenvironment all play important roles in tumor formation. However, there are few reports on the relationships between EMT and these factors. In addition, in recent years, traditional Chinese medicine (TCM) has developed a unique system for treating cancer. In this review, we summarize the crucial signaling pathways associated with the EMT process in cancer patients and discuss the interconnections between EMT and other molecular factors (such as CSCs, VM, and the tumor‐related immune microenvironment). We attempt to identify common regulators that might be potential therapeutic targets to thereby optimize tumor treatment. In addition, we outline recent research on TCM approaches that target EMT and thereby provide a foundation for further research on the exact mechanisms by which TCMs affect EMT in cancer.

Traditional Chinese Medicines as Effective Reversals of Epithelial-Mesenchymal Transition Induced-Metastasis of Colorectal Cancer: Molecular Targets and Mechanisms

“…The Notch signaling is another EMT-activating route, which can be activated by Notch binding to Delta and Jagged ligands (Liu et al, 2018). After activation, the Notch intracellular domain (Notch ICD) is released through a cascade of proteolytic cleavages, which enters the nucleus and triggers CSL (CBF1/Su(H)/Lag-1) transcription factor to express EMT-TFs (Du and Shim, 2016).…”

“…After activation, the Notch intracellular domain (Notch ICD) is released through a cascade of proteolytic cleavages, which enters the nucleus and triggers CSL (CBF1/Su(H)/Lag-1) transcription factor to express EMT-TFs (Du and Shim, 2016). Notch signaling is effective in promoting Snail1 and Snail2 expressions, which binds to E-boxes in the human E-cadherin promoter and inhibits the E-cadherin expression (Liu et al, 2018;Avila-Carrasco et al, 2019). Furthermore, Notch directly stimulates the Slug promoter and subsequently leads to an increase of Slug expression, thereby resulting in transforming to EMT phenotype (Kar et al, 2019).…”

“…Research of the anti-metastatic effect of a large number of TCMs monomer compounds and Chinese medicine formulations based on TCM theory or coming from clinical experience have made considerable progress in recent decades. In this article, we mostly focus on certain bioactive compounds, natural herb extracts, and Chinese herbal recipes (Liu et al, 2018;Dai et al, 2019;Guo et al, 2021) repress the EMT program following their specific characteristics to inhibit the invasion and metastasis of CRC. Among them, there is a high proportion of investigations concentrated on TCMsoriginated monomers and compounds, while a small number of researches reported Chinese medicine formulas or medicinal herb extracts, as specifically shown in Tables 1-3, moreover, the chemical structure of the main TCMs active compounds with anti-metastatic and anti-invasive efficacies were exhibited in Figure 2.…”

“…In addition, TCMs have been shown to be effective in postponing cancer recurrence and suppressing metastasis (Ma et al, 2017;, and improving the living quality of cancer patients (Wang K. et al, 2021). In the combat against metastatic CRC, accumulating evidence demonstrated that TCM monomer compounds and Chinese medicine formulations based on TCM theory can exert inhibitory effects on invasion and metastasis of cancer cells via targetting EMT-related signaling pathways (Liu et al, 2018;Bai et al, 2019;Luo et al, 2019).…”

Biejiajian Pill Inhibits Carcinogenesis and Metastasis via the Akt/GSK-3β/Snail Signaling Pathway in Hepatocellular Carcinoma

“…In view of the pathogenic characteristics of HCC, prevention and treatment principles of TCM involve three aspects, namely, Fuzheng peiben, resolve toxins and dissipate bonds and promote blood circulation to remove blood stasis ( Wang et al, 2015 ). Moreover, an increasing number of studies have used TCM as targeted treatments for EMT-induced cancer progression during recent years ( Liu et al, 2018 ).…”