Calpain2 Upregulation Regulates EMT-Mediated Pancreatic Cancer Metastasis via the Wnt/β-Catenin Signaling Pathway

Abstract

Calpains2 (CAPN2) is a calcium-dependent, non-lysosomal cysteine protease that plays critical roles in normal cellular functions and pathological processes, including tumorigenesis, cancer progression, and metastasis. However, the role and underlying regulatory mechanisms of CAPN2 in pancreatic cancer (PC) are still unknown. We found that CAPN2 is highly expressed in PC tissues and associated with poor PC prognosis by using The Cancer Genome Atlas (TCGA) datasets, Gene Expression Omnibus (GEO) datasets, and PC tissue arrays. CAPN2 downregulation significantly inhibited cell proliferation, migration, and invasion and regulated Wnt/β-catenin signaling pathway-mediated epithelial-mesenchymal transition (EMT) in PC cells. Our findings highlight the significance of CAPN2 in tumor regression and, thus, indicate that CAPN2 could be a promising target for PC treatment.

Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma

“…Interestingly, our study found that members of the PHLDA family can activate the EMT signaling pathway. The EMT signaling pathway is a classic cancer-promoting pathway that leads to the formation of secondary metastatic lesions by activating the movement and invasive ability of tumor cells in many tumors, including pancreatic cancer, prostate cancer, and breast cancer [ 24 , 25 , 26 , 27 ]. Therefore, we speculate that the PH domain of the PHLDA family expression products may be an important factor in activating the EMT signaling pathway, and this activation may be the potential mechanism by which the PHLDA family acts in promoting the occurrence and development of PAAD, which needs further experimental verification.…”

Prognostic value, immune signature and molecular mechanisms of the APOBEC family members APOBEC1, APOBEC3A, APOBEC3G and APOBEC3H in pancreatic adenocarcinoma

“…The “EMT signaling pathway” is a classical cancer-promoting pathway that leads to the formation of secondary metastatic lesions by activating the motor and invasive abilities of tumor cells. It plays a cancer-promoting role in many kinds of tumors, including pancreatic adenocarcinoma, prostate cancer and breast cancer ( Kong et al, 2021 ; Nowak and Bednarek, 2021 ; Zhao et al, 2021 ; Peng et al, 2022 ). The activation of APOBEC3A/3G/3H in the “EMT signaling pathway” may be another mechanism to promote the occurrence and development of PAAD.…”

Prognostic value, immune signature and molecular mechanisms of the SUMO family in pancreatic adenocarcinoma

“…The EMT signaling pathway is a classic cancer-promoting pathway that leads to the formation of secondary metastatic lesions by activating the mobility and invasion ability of tumor cells. It plays an oncogenic role in many tumors, including pancreatic cancer, prostate cancer, and breast cancer ( Kong et al, 2021 ; Nowak and Bednarek, 2021 ; Zhao et al, 2021 ; Peng et al, 2022 ). Therefore, the coexpression characteristics of SUMO family members and various oncogenes and their roles in activating various oncogenic pathways may represent another potential mechanism for the occurrence and development of PAAD.…”