Characterization of Collapsin Response Mediator Protein 2 in Colorectal Cancer Progression in Subjects with Diabetic Comorbidity

Yih-Hsin Chang, Hui Ju Yang, Huan Wen Chen, Chiao Wan Hsiao, Yi Chen Hsieh, Yu Wei Chan, Shu Wen Chang, Wei-Lun Hwang, Wei Shone Chen, Hou Hsuan Cheng, Teh Ying Chou, Fu Pang Chang, Hsiang Ling Ho, Fang Yeh Chu, Yu-Li Lo, Chun Jung Chen, Hui Fang Tsai, Ming Yuh Shiau*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Background: Common demographic risk factors are identified in colorectal cancer (CRC) and type 2 diabetes mellitus (DM), nevertheless, the molecular link and mechanism for CRC-DM comorbidity remain elusive. Dysregulated glycogen synthase kinase-3 beta under metabolic imbalance is suggested to accelerate CRC pathogenesis/progression via regulating collpasin response mediator protein-2 (CRMP2). Accordingly, roles of CRMP2 in CRC and CRC-DM patients were investigated for elucidating the molecular convergence of CRC and DM. Methods: CRMP2 profile in tumor tissues from CRC and CRC-DM patients was investigated to explore the link between CRC and DM etiology. Meanwhile, molecular mechanism of glucose to regulate CRMP2 profile and CRC characteristics was examined in vitro and in vivo. Results: CRMP2 was significantly lower in tumor lesions and associated with advanced tumor stage in CRC-DM patients. Physiological hyperglycemia suppressed CRMP2 expression/activity and augmented malignant characteristics of CRC cells. Hyperglycemia promotes actin de-polymerization, cytoskeleton flexibility and cell proliferation/metastasis by downregulating CRMP2 profile and thus contributes to CRC disease progression. Conclusions: This study uncovers molecular evidence to substantiate and elucidate the link between CRC and T2DM, as well as characterizing the roles of CRMP2 in CRC-DM. Accordingly, altered metabolic adaptations are promising targets for anti-diabetic and cancer strategies.

Original languageEnglish
Article number727
Issue number4
StatePublished - 1 Feb 2022


  • CRMP2
  • Colorectal cancer
  • Hyperglycemia
  • Type 2 diabetes mellitus


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