Volume 7,Issue 3
Research on the Mechanism of Marcks in the Pathogenesis of Digestive System Diseases
Marcks (Myristoylated Alanine-Rich Protein Kinase C Substrate) is broadly expressed across tissues and has emerged as a significant player in the pathogenesis of multiple organ systems. Dysregulation of this protein—whether through genetic alterations at the Marcks locus, aberrant phosphorylation, or unchecked activation of downstream signaling pathways—appears to drive disease development in varied contexts. In this review, we focus specifically on the digestive system, examining how Marcks contributes to hepatocellular carcinoma, cholangiocarcinoma, colorectal cancer, and gastric cancer. Rather than simply cataloging its presence in these malignancies, we dissect the mechanistic underpinnings of Marcks-driven tumor initiation and progression. These findings carry important implications for biomarker discovery and may ultimately inform strategies for clinical diagnosis and treatment.
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[3] Kim J, Shishido T, Jiang X, et al., 1994, Phosphorylation, high ionic strength, and calmodulin reverse the binding of MARCKS to phospholipid vesicles. Journal of Biological Chemistry, 269(45): 28214-28219.
[4] Xu XH, Deng CY, Liu Y, et al., 2014, MARCKS regulates membrane targeting of Rab10 vesicles to promote axon development. Cell research, 24(5): 576-594.
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[6] Yarmola EG, Edison AS, Lenox RH, et al., 2001, Actin filament cross linking by MARCKS: characterization of two actin-binding sites within the phosphorylation site domain. Journal of Biological Chemistry, 276(25): 22351-22358.
[7] Stumpo DJ, Bock CB, Tuttle JS, et al., 1995, MARCKS deficiency in mice leads to abnormal brain development and perinatal death. Proceedings of the National Academy of Sciences, 92(4): 944-948.
[8] Brudvig JJ, Weimer JM, 2015, X MARCKS the spot: myristoylated alanine rich C kinase substrate in neuronal function and disease. Frontiers in cellular neuroscience, 9: 407.
[9] Iioka H, Ueno N, Kinoshita N, 2004, Essential role of MARCKS in cortical actin dynamics during gastrulation movements. The Journal of cell biology, 164(2): 169-174.
[10] Kim SS, Kim JH, Kim HS, et al., 2000, Involvement of the θ-type protein kinase C in translocation of myristoylated alanine-rich C kinase substrate (MARCKS) during myogenesis of chick embryonic myoblasts. Biochemical Journal, 347(1): 139-146.
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[12] Fleming A, Copp AJ, 2000, A genetic risk factor for mouse neural tube defects: defining the embryonic basis. Human molecular genetics, 9(4): 575-581.
[13] Stumpo DJ, Bock CB, Tuttle JS, et al., 1995, MARCKS deficiency in mice leads to abnormal brain development and perinatal death. Proceedings of the National Academy of Sciences, 92(4): 944-948.
[14] Weimer JM, Yokota Y, Stanco A, et al., 2009, MARCKS modulates radial progenitor placement, proliferation and organization in the developing cerebral cortex. Development, 136(17): 2965-2975.
[15] Scarlett CO, Blackshear PJ, 2003, Neuroanatomical development in the absence of PKC phosphorylation of the myristoylated alanine-rich C-kinase substrate (MARCKS) protein. Developmental brain research, 144(1): 25-42.
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[17] Sugiura T, Wang H, Barsacchi R, et al., 2016, MARCKS like protein is an initiating molecule in axolotl appendage regeneration. Nature, 531(7593): 237-240.
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[19] Feng JT, Shang S, Beretta L, 2006, Proteomics for the early detection and treatment of hepatocellular carcinoma. Oncogene, 25(27): 3810-3817.
[20] Naboulsi W, Megger DA, Bracht T, et al., 2016, Quantitative tissue proteomics analysis reveals versican as potential biomarker for early-stage hepatocellular carcinoma. Journal of proteome research, 15(1): 38-47.
[21] Wu J, Yang F, Zhao M, et al., 2023, Antler derived microRNA PC-5p-1090 inhibits HCC cell proliferation, migration, and invasion by targeting MARCKS, SMARCAD1, and SOX9. Functional & Integrative Genomics, 23(2): 156.
[22] Song J, Wang Q, Luo Y, et al., 2015, miR-34c-3p inhibits cell proliferation, migration and invasion of hepatocellular carcinoma by targeting MARCKS. International journal of clinical and experimental pathology, 8(10): 12728.
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[27] Bickeböller M, Tagscherer KE, Kloor M, et al., 2015, Functional characterization of the tumor-suppressor MARCKS in colorectal cancer and its association with survival. Oncogene, 34(9): 1150-1159.
[28] Rombouts K, Carloni V, Mello T, et al., 2013, Myristoylated Alanine Rich protein Kinase C Substrate (MARCKS) expression modulates the metastatic phenotype in human and murine colon carcinoma in vitro and in vivo. Cancer letters, 333(2): 244-252.
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[31] Tang L H, Ye P C, Yao L, et al., 2023, LINC01268 promotes epithelial mesenchymal transition, invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS. World Journal of Gastrointestinal Oncology, 15(8): 1366.
[32] Zhao L, Jiang L, He L, et al., 2019, Identification of a novel cell cycle‐related gene signature predicting survival in patients with gastric cancer. Journal of cellular physiology, 234(5): 6350-6360.
[33] Kim HJ, Hwang SH, Han ME, et al., 2012, LAP2 is widely overexpressed in diverse digestive tract cancers and regulates motility of cancer cells. PLoS One, 7(6): e39482.
[34] Marimuthu A, Subbannayya Y, Sahasrabuddhe NA, et al., 2013, SILAC‐based quantitative proteomic analysis of gastric cancer secretome. PROTEOMICS–Clinical Applications, 7(5-6): 355-366.
[35] Chen CH, Fong LWR, Yu E, et al., 2017, Upregulation of MARCKS in kidney cancer and its potential as a therapeutic target. Oncogene, 36(25): 3588-3598.
[36] Xiu P, Dong X, Dong X, et al., 2013, Secretory clusterin contributes to oxaliplatin resistance by activating Akt pathway in hepatocellular carcinoma. Cancer science, 104(3): 375-382.
[37] Brandi J, Dalla Pozza E, Dando I, et al., 2016, Secretome protein signature of human pancreatic cancer stem-like cells. Journal of proteomics, 136: 1-12.
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