Neuropeptide Y Peptide Family and Cancer: Antitumor Therapeutic Strategies

Abstract

Currently available data on the involvement of neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) and their receptors (YRs) in cancer are updated. The structure and dynamics of YRs and their intracellular signaling pathways are also studied. The roles played by these peptides in 22 different cancer types are reviewed (e.g., breast cancer, colorectal cancer, Ewing sarcoma, liver cancer, melanoma, neuroblastoma, pancreatic cancer, pheochromocytoma, and prostate cancer). YRs could be used as cancer diagnostic markers and therapeutic targets. A high Y1R expression has been correlated with lymph node metastasis, advanced stages, and perineural invasion; an increased Y5R expression with survival and tumor growth; and a high serum NPY level with relapse, metastasis, and poor survival. YRs mediate tumor cell proliferation, migration, invasion, metastasis, and angiogenesis; YR antagonists block the previous actions and promote the death of cancer cells. NPY favors tumor cell growth, migration, and metastasis and promotes angiogenesis in some tumors (e.g., breast cancer, colorectal cancer, neuroblastoma, pancreatic cancer), whereas in others it exerts an antitumor effect (e.g., cholangiocarcinoma, Ewing sarcoma, liver cancer). PYY or its fragments block tumor cell growth, migration, and invasion in breast, colorectal, esophageal, liver, pancreatic, and prostate cancer. Current data show the peptidergic system’s high potential for cancer diagnosis, treatment, and support using Y2R/Y5R antagonists and NPY or PYY agonists as promising antitumor therapeutic strategies. Some important research lines to be developed in the future will also be suggested.

Perineural invasion confers poorer clinical outcomes in patients with T1/T2 intrahepatic cholangiocarcinoma: a single center, retrospective cohort study

“…Furthermore, PNI may serve as a substitute for biological markers of invasive disorders that reflect tumor or stage-specific characteristics substantially. In PNI-positive ICC patients, molecules associated with a poorer prognosis for ICC, such as NPY1R , A1ATD , GPX4 , and KRAS mutations, exhibit elevated levels ( 33 - 36 ). Future research should focus on elucidating the molecular mechanism behind tumor-nerve interactions and PNI-related carcinogenesis.…”

Antitumor Strategies Targeting Peptidergic Systems

“…Many in vitro and in vivo experiments have demonstrated the fundamental roles that peptides and their receptors play in cancer progression [1]. After binding to their respective receptors, peptides promote proliferative and antiproliferative effects in cancer cells: the same peptide (e.g., galanin, orexin) can exert both effects in tumor cells (the reason for this being the G protein type and the subtype of receptor involved, for example, galanin 1, 2, and 3 receptors), whereas other peptides (e.g., substance P, neurotensin) mainly induce a proliferative action (oncogenic effect) in many types of tumor cells [2,3]. Accordingly, peptides and receptor antagonists can be used as potential anticancer drugs, although the latter compounds show a higher therapeutic capacity than peptides [4].…”

Editorial for the Special Issue “Current Research on Cancer Biology and Therapeutics”

“…This Special Issue presents compounds exerting antitumor effects and increases the knowledge on potential and promising anticancer strategies to be used in the near future in clinical practice. These compounds include acetylcorynoline (for colon cancer) [ 2 ], BaP1 (a benzo[a]phenoxazine derivative, for colorectal cancer) [ 3 ], sarco/endoplasmic reticulum calcium ATPase inhibitors (for papillary thyroid carcinoma) [ 4 , 5 ], neuropeptide Y (for liver cancer, Ewing sarcoma, and cholangiocarcinoma) [ 6 ], neuropeptide Y receptor antagonists (for colorectal cancer and breast cancer) [ 6 ], and neurokinin-1 receptor antagonists (for different cancer types) [ 7 ]. These previous studies have opened new lines of research on targetable molecules to explore promising antitumor therapeutic strategies.…”

“…In this Special Issue, two reviews highlight the important role played by peptides in tumor development [ 6 , 7 ]. Both studies were performed by Coveñas and colleagues from the University of Salamanca (Salamanca, Spain).…”

“…The first review was focused on the involvement of the neuropeptide Y peptide family in cancer and on the potential promising anticancer therapeutic strategies that could be applied, and the second review was devoted to the widespread antitumor action exerted by the drug aprepitant, a neurokinin-1 receptor antagonist exclusively used in clinical practice as an antiemetic. The first paper was focused on the involvement of neuropeptide Y, peptide YY, and pancreatic polypeptide in twenty-two different cancer types [ 6 ]. Tumor cell proliferation, migration, invasion/metastasis, and angiogenesis are mediated by neuropeptide Y receptors, the expression of which has been associated with lymph node metastasis, perineural invasion, advanced stages, and tumor growth and survival.…”