IndraLab

Statements

ACVR1 binds PSMD14. 24 / 27
3 | 24
sparser
"In addition, we provide experimental evidence that BMP6 pathway regulated by ALK2-PSMD14 axis induces chemoresistance of human colorectal cancer cells through upregulating ABC transporter genes, and higher expressions of PSMD14 and ALK2 genes are clinically associated with poor prognosis of human colorectal cancer patients."
31685442
sparser
"These findings suggest that the PSMD14-ALK2 axis plays an essential role in initiation of the BMP6 signaling pathway and contributes to tumorigenesis and chemoresistance of colorectal cancers."
31685442
sparser
"The ALK2-PSMD14 axis also plays an important role in the occurrence of colorectal cancer and cancer stem cells [ xref ]."
38863002
sparser
"Co-immunopreciptitation (Co-IP) assays revealed stronger binding of PSMD14 to ALK2 than the other type I receptors, ALK3 and ALK6 ( xref a)."
31685442
sparser
"In fact, immunoprecipitation assays strongly supported the endogenous interaction between PSMD14 and ALK2 upon BMP6 treatment ( xref b)."
31685442
sparser
"PSMD14 bound to ALK2 and increased the level of ALK2 protein at 10 min post BMP6 treatment and this complex was subsequently dissociated ( xref b)."
31685442
sparser
"These results collectively suggest that PSMD14 binds to ALK2 and is involved in the stability of ALK2 through its DUB activity."
31685442
sparser
"This time point was similar to the time point of endogenous ALK2 interaction with PSMD14 ( xref b)."
31685442
sparser
"The PSMD14-ALK2 axis is required for tumorigenesis of colorectal cancer cells."
31685442
sparser
"Although these results support that the PSMD14-ALK2 axis in the BMP6 signaling pathway is involved in tumor growth, it is possible that this axis may affect the migration of colorectal cancers."
31685442
sparser
"These results suggest that the PSMD14-ALK2 axis is required for cell growth, but not cell migration."
31685442
sparser
"Next, we examined the possibility that the PSMD14-ALK2 axis regulates the proliferation of colorectal cancer cells through modulating other target proteins of PSMD14 such as c-Jun, Mitf, and ErbB2 which have been previously reported xref , xref , xref ."
31685442
sparser
"The expression of ErbB2 gene was slightly decreased by PSMD14 depletion whereas it was not affected by ALK2 depletion (Fig. S6a), suggesting that the regulation of ErbB2 protein is independent of the PSMD14-ALK2 axis."
31685442
sparser
"Collectively, our results indicate that the PSMD14-ALK2 axis is not involved in the regulation of c-Jun, ErbB2 and Mitf proteins upon BMP6 treatment."
31685442
sparser
"In addition, PSMD14 depletion in tumor xenografts decreased the expression of endogenous ALK2 protein, together with the decreased expression of target proteins, including phospho-Smad5 and ID3, modulated by the PSMD14-ALK2 axis ( xref f, S7a and b)."
31685442
sparser
"These results demonstrate that the PSMD14-ALK2 axis is responsible for the tumorigenesis of colon cancers."
31685442
sparser
"Since cancer stemness and chemoresistance have been recognized as key factors inducing tumorigenesis and tumor recurrence xref , xref , xref , xref , xref , we next examined whether the PSMD14-ALK2 axis in the BMP6 signaling pathway is involved in cancer stemness and chemoresistance of colorectal cancers."
31685442
sparser
"To further verify an importance of PSMD14-ALK2 axis in chemoresistance, we examined whether expressions of 48 ATP binding cassette (ABC) transporter genes regulated by BMP6."
31685442
sparser
"These results indicate that the PSMD14-ALK2 axis plays a crucial role in cancer stemness and chemoresistance of colon cancers through regulating the BMP6 signaling pathway."
31685442
sparser
"To further support the importance of the PSMD14-ALK2 axis in chemoresistance, however, we have to demonstrate why ABCA7 and ABCC4 genes are induced at 6 h upon BMP6 treatment, because endogenous ALK2 expression was increased at early time and subsequently decreased after 1 h upon BMP6 treatment ( xref b)."
31685442
sparser
"Since our present data indicates that PSMD14 plays an essential role in the BMP6 signaling pathway through deubiquitinating the ALK2 receptor, and this PSMD14-ALK2 axis is required for tumorigenesis and cancer stemness of colon cancers, we next investigated the correlation between PSMD14 and ALK2 expression in colorectal cancer cell lines and public microarray datasets of cancer patients."
31685442
sparser
"We here identified the deubiquitinating enzyme PSMD14 regulating the stability of the ALK2 type I receptor in the BMP6 signaling pathway and thus demonstrated the importance of the PSMD14-ALK2 axis in the BMP6 signaling pathway regarding the proliferation, cancer stemness, and chemoresistance of colon cancers ( xref )."
31685442
sparser
"In conclusion, we here demonstrate that initiation of the BMP6 signaling pathway is driven by the deubiquitinating enzyme PSMD14 targeting the ALK2 receptor, and show the importance of the ALK2-PSMD14 axis in tumorigenesis, cancer stemness and chemoresistance of colon cancers."
31685442
sparser
"In this study, we identified an essential role of deubiquitinating enzyme PSMD14 in the initiation of BMP6 signaling pathway through deubiquitinating the Smurf1-mediated BMP type I receptor ALK2 polyubiquitination and provide a basis for underlying mechanism of BMP6 pathway via ALK2-PSMD14 axis in tumorigenesis and stemness/chemoresistance of human colorectal cancer."
31685442