scholarly journals A late endosome signaling hub that couples PI3Kα and WNT/β-catenin signaling in breast cancer

Author(s):  
Samuel J. Rodgers ◽  
Sabryn A. Hamila ◽  
Christina A. Mitchell ◽  
Lisa M. Ooms
Keyword(s):  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Samuel J. Rodgers ◽  
Lisa M. Ooms ◽  
Viola M. J. Oorschot ◽  
Ralf B. Schittenhelm ◽  
Elizabeth V. Nguyen ◽  
...  

AbstractINPP4B suppresses PI3K/AKT signaling by converting PI(3,4)P2 to PI(3)P and INPP4B inactivation is common in triple-negative breast cancer. Paradoxically, INPP4B is also a reported oncogene in other cancers. How these opposing INPP4B roles relate to PI3K regulation is unclear. We report PIK3CA-mutant ER+ breast cancers exhibit increased INPP4B mRNA and protein expression and INPP4B increased the proliferation and tumor growth of PIK3CA-mutant ER+ breast cancer cells, despite suppression of AKT signaling. We used integrated proteomics, transcriptomics and imaging to demonstrate INPP4B localized to late endosomes via interaction with Rab7, which increased endosomal PI3Kα-dependent PI(3,4)P2 to PI(3)P conversion, late endosome/lysosome number and cargo trafficking, resulting in enhanced GSK3β lysosomal degradation and activation of Wnt/β-catenin signaling. Mechanistically, Wnt inhibition or depletion of the PI(3)P-effector, Hrs, reduced INPP4B-mediated cell proliferation and tumor growth. Therefore, INPP4B facilitates PI3Kα crosstalk with Wnt signaling in ER+ breast cancer via PI(3,4)P2 to PI(3)P conversion on late endosomes, suggesting these tumors may be targeted with combined PI3K and Wnt/β-catenin therapies.


Author(s):  
G. Kasnic ◽  
S. E. Stewart ◽  
C. Urbanski

We have reported the maturation of an intracisternal A-type particle in murine plasma cell tumor cultures and three human tumor cell cultures (rhabdomyosarcoma, lung adenocarcinoma, and osteogenic sarcoma) after IUDR-DMSO activation. In all of these studies the A-type particle seems to develop into a form with an electron dense nucleoid, presumably mature, which is also intracisternal. A similar intracisternal A-type particle has been described in leukemic guinea pigs. Although no biological activity has yet been demonstrated for these particles, on morphologic grounds, and by the manner in which they develop within the cell, they may represent members of the same family of viruses.


Author(s):  
John L. Swedo ◽  
R. W. Talley ◽  
John H. L. Watson

Since the report, which described the ultrastructure of a metastatic nodule of human breast cancer after estrogen therapy, additional ultrastructural observations, including some which are correlative with pertinent findings in the literature concerning mycoplasmas, have been recorded concerning the same subject. Specimen preparation was identical to that in.The mitochondria possessed few cristae, and were deteriorated and vacuolated. They often contained particulates and fibrous structures, sometimes arranged in spindle-shaped bundles, Fig. 1. Another apparent aberration was the occurrence, Fig. 2 (arrows) of linear profiles of what seems to be SER, which lie between layers of RER, and are often recognizably continuous with them.It was noted that the structure of the round bodies, interpreted as within autophagic vacuoles in the previous communication, and of vesicular bodies, described morphologically closely resembled those of some mycoplasmas. Specifically, they simulated or reflected the various stages of replication reported for mycoplasmas grown on solid nutrient. Based on this observation, they are referred to here as “mycoplasma-like” structures, in anticipation of confirmatory evidence from investigations now in progress.


2010 ◽  
Vol 34 (8) ◽  
pp. S49-S49
Author(s):  
Lei Wang ◽  
Xun Zhou ◽  
Lihong Zhou ◽  
Yong Chen ◽  
Xun Zhu ◽  
...  

2010 ◽  
Vol 34 (8) ◽  
pp. S47-S47
Author(s):  
Guopei Zheng ◽  
Sisi Yi ◽  
Yafei Li ◽  
Fangren Kong ◽  
Yanhui Yu ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A741-A741
Author(s):  
P ANG ◽  
D SCHRAG ◽  
K SCHNEIDER ◽  
K SHANNON ◽  
J JOHNSON ◽  
...  

Ob Gyn News ◽  
2005 ◽  
Vol 40 (8) ◽  
pp. 39
Author(s):  
Bruce Jancin
Keyword(s):  

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