1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241000, P.R. China.
2. Department of Urinary Surgery, The Second Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241000, P.R. China.
#These authors contributed equally to this work.
Background: The Hippo pathway's primary kinase component, large tumor suppressor 1 (LATS1), has been hypothesized as a tumor suppressor in a variety of cancers. LATS1's biological effects on colorectal cancer (CRC) are yet to be determined.
Methods: The analysis of LATS1 mRNA expression in CRC was conducted using public databases from the Gene Expressing Profiling Interactive Analysis database (GEPIA). Investigation for the expression of LATS1 protein in 102 CRC tumor tissues and 57 normal tissues was performed using immunohistochemistry (IHC) analysis. In vitro genetic manipulation was used to explore the potential role and mechanism of LATS1 in the regulation of proliferation and migration of CRC cells.
Results: LATS1 was found to be considerably downregulated in CRC tissues, with much lower levels in individuals with bigger tumors of size (≥5 cm), deeper invasion (T3-4), positive lymph node metastasis (LNM), and advanced tumor-node-metastasis (TNM) stage (III-IV). As exhibited by clinical data analysis, LATS1 loss was significantly associated with TNM and LNM staging in CRC patients. Furthermore, our in vitro investigations revealed that LATS1 depletion increased CRC cell proliferation and migration in HCT116 cells, whereas overexpressing LATS1 had the opposite effect in SW620 cells. LATS1 suppressed the expression of glioma-associated oncogene-1 (Gli1), and LATS1's tumor-suppressive actions in CRC are dependent on Gli1. Moreover, LATS1 could modulate Yes-associated protein 1 (YAP1) expression and mTOR activation in CRC cells.
Conclusion: Our findings identify the LATS1 as a unique Gli1 regulator in CRC cell migration and proliferation, and suggest that LATS1 may serve as a potential therapeutic target for CRC.
Keywords: LATS1, proliferation, migration, Gli1, colorectal cancer