SOX8 promotes cetuximab resistance via HGF/MET bypass pathway activation in colorectal cancer

Piao, Haiyan; Qu, Junle; Liu, Yun-Peng

doi:10.1007/s00280-021-04378-z

Cited by 6 publications

(4 citation statements)

References 37 publications

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“…Because the affinity of PROTACs is not as high as that required by small molecular inhibitors, and it can be reused, it can better deal with the drug resistance caused by these mechanisms. Another kind of drug resistance is achieved through the bypass signal pathway 160 . Because the degradation of target proteins by PROTACs is immediate and lasting, it can kill cells before they adapt to the pressure, which is an advantage compared with small molecules.…”

Section: Discussion and Perspectivementioning

confidence: 99%

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From classic medicinal chemistry to state‐of‐the‐art interdisciplinary medicine: Recent advances in proteolysis‐targeting chimeras technology

Zhao

Chen

Huang

et al. 2023

Interdisciplinary Medicine

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Proteolysis-targeting chimeras (PROTACs) is a targeted protein degradation (TPD) technique effected by hijacking the ubiquitin-proteasome system (UPS) of the cells. A PROTAC molecule specifically binds to its protein of interest (POI) and recruits an E3 ligase to assemble a ternary complex. The POI was subsequently ubiquitinated, followed by being degraded by proteasomes. After 20 years of development, PROTAC technology has made a significant progress, and quite some candidates have entered clinical trials. Along with the excitement of realizing that PROTAC technology can develop therapeutics toward those traditionally believed "undruggable" targets; there are still unmet demands in PROTAC design, screening, and intracellular availability. PROTAC technology is rapidly advancing from employing traditional medicinal chemistry methodologies to integrating state-of-the-art chemical biology technologies, becoming a typical example of interdisciplinary medicine. This review summarizes the progress made in PROTAC technology in recent years, including expanding new targets, developing dual-target PROTACs, rational design and screening strategies, regulatory activation, targeted delivery, and developing biological macromolecule-contained PROTACs.

show abstract

Section: Discussion and Perspectivementioning

confidence: 99%

“…Another kind of drug resistance is achieved through the bypass signal pathway. 160 Because the degradation of target proteins by PROTACs is immediate and lasting, it can kill cells before they adapt to the pressure, which is an advantage compared with small molecules.…”

Section: Discussion and Perspectivementioning

confidence: 99%

From classic medicinal chemistry to state‐of‐the‐art interdisciplinary medicine: Recent advances in proteolysis‐targeting chimeras technology

Zhao

Chen

Huang

et al. 2023

Interdisciplinary Medicine

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“…Subsequently, SOX8 levels in SW620 cells were upregulated, followed by silencing USP29, after which SW620 cell proliferation was promoted. SOX8 activates the HGF/MET axis to diminish the sensitivity of CRC cells to cetuximab [ 39 ]. Furthermore, Wang et al reported that the upregulation of SOX8 is positively correlated with the TNM stage I and II stages and a poor overall survival of CRC patients [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Promotive role of USP29-mediated deubiquitination in malignant proliferation of colorectal cancer cells via the KIAA1429/SOX8 axis

Jiang

Chen

et al. 2022

Bosn J of Basic Med Sci

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Colorectal cancer (CRC) is regarded as one of the most prevalent neoplasms worldwide, and ubiquitination and N6-methyladenosine (m6A) modification regulate the outgrowth of multiple cancers. This study attempted to explore the effect of ubiquitin-specific peptidases 29 (USP29) on the malignant proliferation of CRC cells via stabilizing Vir-like m6A methyltransferase associated (VIRMA/KIAA1429). First, upregulations of USP29, KIAA1429, and SRY-box transcription factor 8 (SOX8) were found in CRC tissues and cells through real-time quantitative polymerase chain reaction and Western blotting. After transfection of si-USP29, the proliferation of CRC cells was evaluated by the cell counting kit-8, colony formation and 5-ethynyl-2’-deoxyuridine assays, and we observed that depletion of USP29 inhibited the proliferation of CRC cells. Co-immunoprecipitation confirmed the binding of USP29 to KIAA1429. Mechanically, USP29 mediated deubiquitination to stabilize the protein levels of KIAA1429, and KIAA1429 promoted the stability of SOX8 mRNA through m6A modification. Moreover, overexpression of KIAA1429 or SOX8 reversed the inhibitory effects of USP29 depletion on CRC cell proliferation. Finally, the xenograft tumor model revealed the promotive role of USP29 in the proliferation of CRC cells in vivo. Altogether, USP29 facilitates the malignant proliferation of CRC cells via upregulating the KIAA1429/SOX8 axis.

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“…The activation of HGF/MET/ CD44 signaling has been reported to promote metastasis CRC resistance to EGFR inhibitors (Joosten et al, 2020). Additionally, upregulated HGF was found to induce cetuximab resistance in CRC cells via the binding with SRY-Box Transcription Factor 8 (SOX8), indicating the crucial role of SOX8/HGF/MET in the CRC therapy resistance (Piao et al, 2022). Preclinical and clinical findings suggested that EGFR/MET activation through HGF-induced cetuximab resistance (Liska et al, 2011;Takahashi et al, 2014;Yonesaka et al, 2015).…”

Section: Strategies To Overcome Resistance Caused By Mutations In Egf...mentioning

confidence: 99%

Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling

Albadari,

Xie,

2024

Front. Pharmacol.

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In 2023, colorectal cancer (CRC) is the third most diagnosed malignancy and the third leading cause of cancer death worldwide. At the time of the initial visit, 20% of patients diagnosed with CRC have metastatic CRC (mCRC), and another 25% who present with localized disease will later develop metastases. Despite the improvement in response rates with various modulation strategies such as chemotherapy combined with targeted therapy, radiotherapy, and immunotherapy, the prognosis of mCRC is poor, with a 5-year survival rate of 14%, and the primary reason for treatment failure is believed to be the development of resistance to therapies. Herein, we provide an overview of the main mechanisms of resistance in mCRC and specifically highlight the role of drug transports, EGFR, and HGF/c-MET signaling pathway in mediating mCRC resistance, as well as discuss recent therapeutic approaches to reverse resistance caused by drug transports and resistance to anti-EGFR blockade caused by mutations in EGFR and alteration in HGF/c-MET signaling pathway.

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SOX8 promotes cetuximab resistance via HGF/MET bypass pathway activation in colorectal cancer

Cited by 6 publications

References 37 publications

From classic medicinal chemistry to state‐of‐the‐art interdisciplinary medicine: Recent advances in proteolysis‐targeting chimeras technology

From classic medicinal chemistry to state‐of‐the‐art interdisciplinary medicine: Recent advances in proteolysis‐targeting chimeras technology

Promotive role of USP29-mediated deubiquitination in malignant proliferation of colorectal cancer cells via the KIAA1429/SOX8 axis

Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling

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