Regulation of secretory pathway kinase or kinase-like proteins inhuman cancers

Sep 24, 2026

Reviewing secretory pathway kinase or kinase-like proteins (SPKKPs), this article explains how these ER-, Golgi-, and extracellular-located kinases regulate secretory signaling and affect tumorigenesis. It highlights phosphorylation-driven control of substrates that shape tumor growth, metastasis, and immune-related progression. The review further summarizes evidence that SPKKP expression in human cancers is modulated by multiple factors, and discusses recent advances with emphasis on targeting SPKKPs as a potential immunotherapy-enabled anticancer strategy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Secretory pathway

TYPE Review PUBLISHED 07 February 2023 DOI 10.3389/fimmu.2023.942849 OPEN ACCESS EDITED BY Zhaohua Hou, Memorial Sloan Kettering Cancer Center, United States REVIEWED BY Tan-Huy Chu, Pham Ngoc Thach University of Medicine, Vietnam Yongye Huang, Northeastern University, China Qi Su, University of California, San Diego, United States *CORRESPONDENCE Shu Guan [guanshu1987@163.com](guanshu1987@163.com) †These authors have contributed equally to this work SPECIALTY SECTION This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology RECEIVED 13 May 2022 ACCEPTED 24 January 2023 PUBLISHED 07 February 2023 CITATION Du S, Zhu C, Ren X, Chen X, Cui X and Guan S (2023) Regulation of secretory pathway kinase or kinase-like proteins inhuman cancers. Front. Immunol. 14:942849 . doi: 10.3389/fimmu.2023.942849 COPYRIGHT © 2023 Du, Zhu, Ren, Chen, Cui and Guan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Regulation of secretory pathway kinase or kinase-like proteins inhuman cancers Shaonan Du 1†, Chen Zhu 2†, Xiaolin Ren 3, Xin Chen 1, Xiao Cui 2 and Shu Guan 4* 1 Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China, 2 Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, China, 3 Department of Neurosurgery, Shenyang Red Cross Hospital, Shenyang, China, 4 Department of Surgical Oncology and Breast Surgery, The First Hospital of China Medical University, Shenyang, China Secretory pathway kinase or kinase-like proteins (SPKKPs) are effective in the lumen of the endoplasmic reticulum (ER), Golgi apparatus (GA), and extracellular space. These proteins are involved in secretory signaling pathways and are distinctive from typical protein kinases. Various reports have shown that SPKKPs regulate the tumor igenesis and progression of human cancer via the phosphorylation of various substrates, which is essential in physiological and pathological processes. Emerging evidence has revealed that the expression of SPKKPs in human cancers is regulated by multiple factors. This review summarizes the current understanding of the contribution of SPKKPs in tumorigenesis and the progression of immunity. With the epidemic trend of immunotherapy, targeting SPKKPs may be a novel approach to anticancer therapy. This study brieﬂy discusses the recent advances regarding SPKKPs. KEYWORDS secretory pathway, kinase, SPKKPs, tumor, microenvironment 1 Introduction Kinases are evolutionarily conserved enzymes for the regulation of many cellular processes by transferring phosphate molecules from ATP to target substrates (1, 2) . The human kinome encompasses more than 500 kinases and acts as molecular activators and signal transducers. Solid tumors, among other disorders, present defective and abnormal activation of kinases (3) . It has been identiﬁed in recent years that a group of proteins, the“secretory pathway kinase or kinase-like proteins” (SPKKPs), is explicitly observed in the Abbreviations: SPKKPs, secretory pathway kinase or kinase-like proteins; ER, endoplasmic reticulum; GA, Golgi apparatus; AXER, ATP/ADP exchanger on the endoplasmic reticulum membrane; PDI, protein disulﬁdeisomerase; UPR, unfolded protein response; ERAD, ER-related degradation; TGN, trans-Golgi network; GSCs, glioblastoma stem cells; HCC, hepatocellular carcinoma; GAG, glycosaminoglycan; LEF, lymphoid enhancer factor; CRC, colorectal cancer; NPC, nasopharyngeal carcinoma; PV1, peptide vaccine; MMP, matrix me

FAQs

What are secretory pathway kinase or kinase-like proteins (SPKKPs)?

SPKKPs are proteins observed in the lumen of the endoplasmic reticulum (ER), Golgi apparatus (GA), and extracellular space, distinct from typical protein kinases. They participate in secretory signaling pathways.

How do SPKKPs contribute to cancer progression?

SPKKPs can phosphorylate multiple substrates involved in pathological processes, including tumor growth and metastasis. Bioinformatic analyses described in the review indicate a tumor-promoting phenotype for most SPKKPs.

Why might targeting SPKKPs be a promising anticancer approach?

The review notes that SPKKPs expression is regulated by multiple factors in human cancers and summarizes recent advances. With the immunotherapy trend, targeting SPKKPs is proposed as a novel strategy to combat cancers.

Sep 24, 2026

Upload by CatatanPagi