Carboxypeptidase E promotes cancer cell survival, but inhibits migration and invasion

Abstract

Carboxypeptidase E (CPE), a prohormone processing enzyme is highly expressed and secreted from (neuro)endocrine tumors and gliomas, and has been implicated in cancer progression by promoting tumor growth. Our study demonstrates that secreted or exogenously applied CPE promotes survival of pheochromocytoma (PC12) and hepatocellular carcinoma (MHCC97H) cells under nutrient starvation and hypoxic conditions, but had no effect on their proliferation. CPE also reduced migration and invasion of fibrosarcoma (HT1080) cells. We show that CPE treatment mediates survival of MHCC97H cells during metabolic stress by up-regulating the expression of anti-apoptotic protein BCL-2, and other pro-survival genes, via activation of the ERK1/2 pathway.

Downregulation of Talin1 promotes hepatocellular carcinoma progression through activation of the ERK1/2 pathway

“…In addition, we found that Talin1 inhibition significantly reduced proliferation of HCC cells, consistent with another study in which Talin1‐knockdown MHCC‐97L cells were significantly more blocked in G 0 /G 1 phase . Some genes also have analogous characteristics, possessing diverse and complex biological functions in regulating tumor progression through distinct pathways . For example, SPARC suppresses glioblastoma cell growth by interfering with growth factor–growth factor receptor interactions, while promoting cell migration and invasion by activating integrin‐regulated kinases including integrin‐linked kinase and FAK, and signaling .…”

Carboxypeptidase E (CPE) inhibits the secretion and activity of Wnt3a

“…17,8 CPE has also been implicated in cancer progression [18][19][20][21] and as a neuro-trophic factor regulating brain functions. [22][23][24][25][26] Lately, it was found that CPE is also involved in other biological processes such as bone homeostasis 27 and bowel disease.…”

“…6 In both cases, CPE functions as an antiproliferation regulator by interfering with the Wnt pathway. However, it has been shown that under hypoxic conditions CPE can promote cancer cell survival 20 implying that it has pro-survival activities as well. Thus, CPE may have a dual effect on the regulation of the Wnt pathway.…”

“…After 24 h, the cells were fixed and visualized by a confocal microscope. (b) HEK293T cells were co-transfected with the HA-Wnt3a vector and GFP-peptide(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) or Scr as a control. Forty-eight hours post transfection, cells were harvested and IP assay was performed using an anti-HA antibody.…”

Carboxypeptidase E (NF-α1): a new trophic factor in neuroprotection

“…Since the pattern of the CPE-induced activation of the ERK and Akt signaling pathways is similar to classic trophic factors such as BDNF and NGF, an alternative name was given to CPE, “Neurotrophic Factor-α1” (NF-α1), indicating its functions as a trophic factor. In addition to primary cultured neurons, a recent study further found that secreted NF-α1 protects PC12 cells, a pheochromocytoma cell line, against starvation- and hypoxia-induced cell death [22] .…”