S-palmitoylation of PCSK9 induces sorafenib resistance in liver cancer by activating the PI3K/AKT pathway

Sun, Yan; Zhang, Huan; Meng, Junpeng; Guo, Feng; Ren, Dianyun; Wu, Heshui; Jin, Xin

doi:10.1016/j.celrep.2022.111194

Cited by 49 publications

(25 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Abdelwahed et al 56,58 have reported that inhibition of PCSK9 suppressed tumour angiogenesis in prostate cancer. Interestingly, another study has linked PCSK9 overexpression to resistance against sorafenib, an anti-angiogenic agent, in HCC 59 . However, this study has not examined the role of PCSK9 in vessel co-option.…”

Section: Discussionmentioning

confidence: 99%

High levels of serum cholesterol positively correlate with the risk of the development of vessel co-opting tumours in colorectal cancer liver metastases

Rada

Krzywon

Kapelanski-Lamoureux

et al. 2022

Preprint

View full text Add to dashboard Cite

Colorectal cancer liver metastatic (CRCLM) tumours present as two main histopathological growth patterns (HGPs) including desmoplastic HGP (DHGP) and replacement HGP (RHGP). The DHGP tumours obtain their blood supply by sprouting angiogenesis, whereas the RHGP tumours utilize an alternative vascularisation known as vessel co-option. In vessel co-option, the cancer cells hijack the mature sinusoidal vessels to obtain blood supply. Vessel co-option has been reported as an acquired mechanism of resistance to anti-angiogenic treatment in CRCLM. Here, we show the connection between the concentration of serum cholesterol and the development of vessel co-option in CRCLM. Our clinical data suggested that the elevation of serum cholesterol levels correlates with the risk of developing vessel co-opting tumours. Moreover, inhibition of the key modulators of cholesterol metabolism including HMGCR or PCSK9 attenuated the development of CRCLM tumours, as well as vessel co-option in vivo. Altogether, our data uncovered the importance of cholesterol in the development of vessel co-option tumours and demonstrated PCSK9 and HMGCR inhibitors as promising strategies to mitigate the development of vessel co-option tumours in CRCLM.

show abstract

Section: Discussionmentioning

confidence: 99%

High levels of serum cholesterol positively correlate with the risk of the development of vessel co-opting tumours in colorectal cancer liver metastases

Rada

Krzywon

Kapelanski-Lamoureux

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Oncoproteins such as RAS-family GTPases require palmitoylation to promote tumor formation. 93 Sun et al 94 designed a peptide containing a mutant site to compete for S-palmitoylation of PCSK9 in vivo, and confirmed that the inhibitor enhanced the inhibitory effect of sorafenib on hepatoma cells by both in vivo and in vitro experiments. 94 The data suggest that some uncommon PTMs may also have clinical significance in HCC.…”

Section: Discussionmentioning

confidence: 90%

Diagnostic and Prognostic Value of Protein Post-Translational Modifications in Hepatocellular Carcinoma

Wang¹,

Wang²,

Wang³

et al. 2023

J Clin Transl Hepatol

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a common malignant tumor with high incidence and cancer mortality worldwide. Post-translational modifications (PTMs) of proteins have a great impact on protein function. Almost all proteins can undergo PTMs, including phosphorylation, acetylation, methylation, glycosylation, ubiquitination, and so on. Many studies have shown that PTMs are related to the occurrence and development of cancers. The findings provide novel therapeutic targets for cancers, such as glypican-3 and mucin-1. Other clinical implications are also found in the studies of PTMs. Diagnostic or prognostic value, and response to therapy have been identified. In HCC, it has been shown that glycosylated alpha-fetoprotein (AFP) has a higher detection rate for early liver cancer than conventional AFP. In this review, we mainly focused on the diagnostic and prognostic value of PTM, in order to provide new insights into the clinical implication of PTM in HCC.

show abstract

“…The Kaplan-Meier curve indicated that high PCSK9 expression correlates with poor response to sorafenib in patients with HCC. According to Sun et al ., the suppression of S-palmitoylation by PCSK9 sensitized sorafenib therapy in HCC 68 . The anthelmintic agent mebendazole augments the sensitivity of HCC cells to sorafenib by targeting BCL2 and MAPK 69 .…”

Section: Discussionmentioning

confidence: 99%

Drug Repurposing Flubendazole to Suppress Tumorigenicity via PCSK9-dependent Inhibition and Potentiate Lenvatinib Therapy for Hepatocellular Carcinoma

Jin¹,

Yu²,

Shao‐Horn³

et al. 2023

Int. J. Biol. Sci.

View full text Add to dashboard Cite

S-palmitoylation of PCSK9 induces sorafenib resistance in liver cancer by activating the PI3K/AKT pathway

Cited by 49 publications

References 50 publications

High levels of serum cholesterol positively correlate with the risk of the development of vessel co-opting tumours in colorectal cancer liver metastases

High levels of serum cholesterol positively correlate with the risk of the development of vessel co-opting tumours in colorectal cancer liver metastases

Diagnostic and Prognostic Value of Protein Post-Translational Modifications in Hepatocellular Carcinoma

Drug Repurposing Flubendazole to Suppress Tumorigenicity via PCSK9-dependent Inhibition and Potentiate Lenvatinib Therapy for Hepatocellular Carcinoma

Contact Info

Product

Resources

About