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Angiopoietin-like protein 2 renders colorectal cancer cells resistant to chemotherapy by activating spleen tyrosine kinase-phosphoinositide 3-kinase-dependent anti-apoptotic signaling.

Horiguchi H, Endo M, Miyamoto Y, Sakamoto Y, Odagiri H, Masuda T, Kadomatsu T, Tanoue H, Motokawa I, Terada K, Morioka MS, Manabe I, Baba H, Oike Y - Cancer Sci. (2014)

Bottom Line: Apoptosis induced by antineoplastic drug treatment was significantly decreased in SW480/ANGPTL2 compared to control cells.Expression of anti-apoptotic BCL-2 family genes was upregulated in SW480/ANGPTL2 compared to SW480/Ctrl cells.To assess signaling downstream of ANGPTL2 underlying this effect, we carried out RNA sequencing analysis of SW480/ANGPTL2 and SW480/Ctrl cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

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Model of tumor cell resistance to antineoplastic therapy through angiopoietin-like protein 2 (ANGPTL2) expression. Tumor cell-secreted ANGPTL2 induces spleen tyrosine kinase (Syk), which activates phosphoinositide 3-kinase (PI3K) and nuclear factor of activated T cells c (NFATc). The PI3K pathway activates nuclear factor-κB (NF-κB) signaling and induces expression of anti-apoptotic BCL-2 family members to inhibit apoptosis. In addition, ANGPTL2 upregulates itself through NFATc.
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fig07: Model of tumor cell resistance to antineoplastic therapy through angiopoietin-like protein 2 (ANGPTL2) expression. Tumor cell-secreted ANGPTL2 induces spleen tyrosine kinase (Syk), which activates phosphoinositide 3-kinase (PI3K) and nuclear factor of activated T cells c (NFATc). The PI3K pathway activates nuclear factor-κB (NF-κB) signaling and induces expression of anti-apoptotic BCL-2 family members to inhibit apoptosis. In addition, ANGPTL2 upregulates itself through NFATc.

Mentions: In summary, we have shown that ANGPTL2 promotes CRC cell survival after antineoplastic drug treatment by regulating anti-apoptotic BCL-2 family genes through Syk–PI3K signaling. Furthermore, ANGPTL2 positively autoregulated its own expression through the Syk–NFAT pathway (Fig. 7). We also showed that CRC cells expressing relatively high levels of ANGPTL2 may develop resistance to chemotherapy. These findings possibly suggest novel approaches to counteracting chemoresistance based on attenuating ANGPTL2 signaling in tumor cells.


Angiopoietin-like protein 2 renders colorectal cancer cells resistant to chemotherapy by activating spleen tyrosine kinase-phosphoinositide 3-kinase-dependent anti-apoptotic signaling.

Horiguchi H, Endo M, Miyamoto Y, Sakamoto Y, Odagiri H, Masuda T, Kadomatsu T, Tanoue H, Motokawa I, Terada K, Morioka MS, Manabe I, Baba H, Oike Y - Cancer Sci. (2014)

Model of tumor cell resistance to antineoplastic therapy through angiopoietin-like protein 2 (ANGPTL2) expression. Tumor cell-secreted ANGPTL2 induces spleen tyrosine kinase (Syk), which activates phosphoinositide 3-kinase (PI3K) and nuclear factor of activated T cells c (NFATc). The PI3K pathway activates nuclear factor-κB (NF-κB) signaling and induces expression of anti-apoptotic BCL-2 family members to inhibit apoptosis. In addition, ANGPTL2 upregulates itself through NFATc.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317964&req=5

fig07: Model of tumor cell resistance to antineoplastic therapy through angiopoietin-like protein 2 (ANGPTL2) expression. Tumor cell-secreted ANGPTL2 induces spleen tyrosine kinase (Syk), which activates phosphoinositide 3-kinase (PI3K) and nuclear factor of activated T cells c (NFATc). The PI3K pathway activates nuclear factor-κB (NF-κB) signaling and induces expression of anti-apoptotic BCL-2 family members to inhibit apoptosis. In addition, ANGPTL2 upregulates itself through NFATc.
Mentions: In summary, we have shown that ANGPTL2 promotes CRC cell survival after antineoplastic drug treatment by regulating anti-apoptotic BCL-2 family genes through Syk–PI3K signaling. Furthermore, ANGPTL2 positively autoregulated its own expression through the Syk–NFAT pathway (Fig. 7). We also showed that CRC cells expressing relatively high levels of ANGPTL2 may develop resistance to chemotherapy. These findings possibly suggest novel approaches to counteracting chemoresistance based on attenuating ANGPTL2 signaling in tumor cells.

Bottom Line: Apoptosis induced by antineoplastic drug treatment was significantly decreased in SW480/ANGPTL2 compared to control cells.Expression of anti-apoptotic BCL-2 family genes was upregulated in SW480/ANGPTL2 compared to SW480/Ctrl cells.To assess signaling downstream of ANGPTL2 underlying this effect, we carried out RNA sequencing analysis of SW480/ANGPTL2 and SW480/Ctrl cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Show MeSH
Related in: MedlinePlus